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Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Review Article

Microglia PTK2B/Pyk2 in the Pathogenesis of Alzheimer’s Disease

Author(s): Yun Guo, Cheng-Kun Sun, Lian Tang and Meng-Shan Tan*

Volume 20, Issue 10, 2023

Published on: 06 February, 2024

Page: [692 - 704] Pages: 13

DOI: 10.2174/0115672050299004240129051655

Price: $65

Abstract

Alzheimer’s disease (AD) is a highly hereditary disease with complex genetic susceptibility factors. Extensive genome-wide association studies have established a distinct susceptibility link between the protein tyrosine kinase 2β (PTK2B) gene and late-onset Alzheimer’s disease (LOAD), but the specific pathogenic mechanisms remain incompletely understood. PTK2B is known to be expressed in neurons, and recent research has revealed its more important significance in microglia. Elucidating the role of PTK2B high expression in microglia in AD’s progression is crucial for uncovering novel pathogenic mechanisms of the disease. Our review of existing studies suggests a close relationship between PTK2B/proline-rich tyrosine kinase 2 (Pyk2) and tau pathology, and this process might be β-amyloid (Aβ) dependence. Pyk2 is hypothesized as a pivotal target linking Aβ and tau pathologies. Concurrently, Aβ-activated Pyk2 participates in the regulation of microglial activation and its proinflammatory functions. Consequently, it is reasonable to presume that Pyk2 in microglia contributes to amyloid-induced tau pathology in AD via a neuroinflammatory pathway. Furthermore, many things remain unclear, such as identifying the specific pathways that lead to the release of downstream inflammatory factors due to Pyk2 phosphorylation and whether all types of inflammatory factors can activate neuronal kinase pathways. Additionally, further in vivo experiments are essential to validate this hypothesized pathway. Considering PTK2B/Pyk2’s potential role in AD pathogenesis, targeting this pathway may offer innovative and promising therapeutic approaches for AD.

[1]
Winblad, B.; Amouyel, P.; Andrieu, S.; Ballard, C.; Brayne, C.; Brodaty, H.; Cedazo-Minguez, A.; Dubois, B.; Edvardsson, D.; Feldman, H.; Fratiglioni, L.; Frisoni, G.B.; Gauthier, S.; Georges, J.; Graff, C.; Iqbal, K.; Jessen, F.; Johansson, G.; Jönsson, L.; Kivipelto, M.; Knapp, M.; Mangialasche, F.; Melis, R.; Nordberg, A.; Rikkert, M.O.; Qiu, C.; Sakmar, T.P.; Scheltens, P.; Schneider, L.S.; Sperling, R.; Tjernberg, L.O.; Waldemar, G.; Wimo, A.; Zetterberg, H. Defeating Alzheimer’s disease and other dementias: A priority for European science and society. Lancet Neurol., 2016, 15(5), 455-532.
[http://dx.doi.org/10.1016/S1474-4422(16)00062-4] [PMID: 26987701]
[2]
Reiman, E.M.; McKhann, G.M.; Albert, M.S.; Sperling, R.A.; Petersen, R.C.; Blacker, D. Alzheimer’s disease: Implications of the updated diagnostic and research criteria. J. Clin. Psychiatry, 2011, 72(9), 1190-1196.
[http://dx.doi.org/10.4088/JCP.10087co1c] [PMID: 21951985]
[3]
Bertram, L.; Lange, C.; Mullin, K.; Parkinson, M.; Hsiao, M.; Hogan, M.F.; Schjeide, B.M.M.; Hooli, B.; DiVito, J.; Ionita, I.; Jiang, H.; Laird, N.; Moscarillo, T.; Ohlsen, K.L.; Elliott, K.; Wang, X.; Hu-Lince, D.; Ryder, M.; Murphy, A.; Wagner, S.L.; Blacker, D.; Becker, K.D.; Tanzi, R.E. Genome-wide association analysis reveals putative Alzheimer’s disease susceptibility loci in addition to APOE. Am. J. Hum. Genet., 2008, 83(5), 623-632.
[http://dx.doi.org/10.1016/j.ajhg.2008.10.008] [PMID: 18976728]
[4]
Scheltens, P.; De Strooper, B.; Kivipelto, M.; Holstege, H.; Chételat, G.; Teunissen, C.E.; Cummings, J.; van der Flier, W.M. Alzheimer’s disease. Lancet, 2021, 397(10284), 1577-1590.
[http://dx.doi.org/10.1016/S0140-6736(20)32205-4] [PMID: 33667416]
[5]
Bellenguez, C.; Küçükali, F.; Jansen, I.E.; Kleineidam, L.; Moreno-Grau, S.; Amin, N.; Naj, A.C.; Campos-Martin, R.; Grenier-Boley, B.; Andrade, V.; Holmans, P.A.; Boland, A.; Damotte, V.; van der Lee, S.J.; Costa, M.R.; Kuulasmaa, T.; Yang, Q.; de Rojas, I.; Bis, J.C.; Yaqub, A.; Prokic, I.; Chapuis, J.; Ahmad, S.; Giedraitis, V.; Aarsland, D.; Garcia-Gonzalez, P.; Abdelnour, C.; Alarcón-Martín, E.; Alcolea, D.; Alegret, M.; Alvarez, I.; Álvarez, V.; Armstrong, N.J.; Tsolaki, A.; Antúnez, C.; Appollonio, I.; Arcaro, M.; Archetti, S.; Pastor, A.A.; Arosio, B.; Athanasiu, L.; Bailly, H.; Banaj, N.; Baquero, M.; Barral, S.; Beiser, A.; Pastor, A.B.; Below, J.E.; Benchek, P.; Benussi, L.; Berr, C.; Besse, C.; Bessi, V.; Binetti, G.; Bizarro, A.; Blesa, R.; Boada, M.; Boerwinkle, E.; Borroni, B.; Boschi, S.; Bossù, P.; Bråthen, G.; Bressler, J.; Bresner, C.; Brodaty, H.; Brookes, K.J.; Brusco, L.I.; Buiza-Rueda, D.; Bûrger, K.; Burholt, V.; Bush, W.S.; Calero, M.; Cantwell, L.B.; Chene, G.; Chung, J.; Cuccaro, M.L.; Carracedo, Á.; Cecchetti, R.; Cervera-Carles, L.; Charbonnier, C.; Chen, H.H.; Chillotti, C.; Ciccone, S.; Claassen, J.A.H.R.; Clark, C.; Conti, E.; Corma-Gómez, A.; Costantini, E.; Custodero, C.; Daian, D.; Dalmasso, M.C.; Daniele, A.; Dardiotis, E.; Dartigues, J.F.; de Deyn, P.P.; de Paiva Lopes, K.; de Witte, L.D.; Debette, S.; Deckert, J.; del Ser, T.; Denning, N.; DeStefano, A.; Dichgans, M.; Diehl-Schmid, J.; Diez-Fairen, M.; Rossi, P.D.; Djurovic, S.; Duron, E.; Düzel, E.; Dufouil, C.; Eiriksdottir, G.; Engelborghs, S.; Escott-Price, V.; Espinosa, A.; Ewers, M.; Faber, K.M.; Fabrizio, T.; Nielsen, S.F.; Fardo, D.W.; Farotti, L.; Fenoglio, C.; Fernández- Fuertes, M.; Ferrari, R.; Ferreira, C.B.; Ferri, E.; Fin, B.; Fischer, P.; Fladby, T.; Fließbach, K.; Fongang, B.; Fornage, M.; Fortea, J.; Foroud, T.M.; Fostinelli, S.; Fox, N.C.; Franco-Macías, E.; Bullido, M.J.; Frank-García, A.; Froelich, L.; Fulton-Howard, B.; Galimberti, D.; García-Alberca, J.M.; García-González, P.; Garcia- Madrona, S.; Garcia-Ribas, G.; Ghidoni, R.; Giegling, I.; Giorgio, G.; Goate, A.M.; Goldhardt, O.; Gomez-Fonseca, D.; González-Pérez, A.; Graff, C.; Grande, G.; Green, E.; Grimmer, T.; Grünblatt, E.; Grunin, M.; Gudnason, V.; Guetta-Baranes, T.; Haapasalo, A.; Hadjigeorgiou, G.; Haines, J.L.; Hamilton-Nelson, K.L.; Hampel, H.; Hanon, O.; Hardy, J.; Hartmann, A.M.; Hausner, L.; Harwood, J.; Heilmann-Heimbach, S.; Helisalmi, S.; Heneka, M.T.; Hernández, I.; Herrmann, M.J.; Hoffmann, P.; Holmes, C.; Holstege, H.; Vilas, R.H.; Hulsman, M.; Humphrey, J.; Biessels, G.J.; Jian, X.; Johansson, C.; Jun, G.R.; Kastumata, Y.; Kauwe, J.; Kehoe, P.G.; Kilander, L.; Ståhlbom, A.K.; Kivipelto, M.; Koivisto, A.; Kornhuber, J.; Kosmidis, M.H.; Kukull, W.A.; Kuksa, P.P.; Kunkle, B.W.; Kuzma, A.B.; Lage, C.; Laukka, E.J.; Launer, L.; Lauria, A.; Lee, C.Y.; Lehtisalo, J.; Lerch, O.; Lleó, A.; Longstreth, W., Jr; Lopez, O.; de Munain, A.L.; Love, S.; Löwemark, M.; Luckcuck, L.; Lunetta, K.L.; Ma, Y.; Macías, J.; MacLeod, C.A.; Maier, W.; Mangialasche, F.; Spallazzi, M.; Marquié, M.; Marshall, R.; Martin, E.R.; Montes, A.M.; Rodríguez, C.M.; Masullo, C.; Mayeux, R.; Mead, S.; Mecocci, P.; Medina, M.; Meggy, A.; Mehrabian, S.; Mendoza, S.; Menéndez-González, M.; Mir, P.; Moebus, S.; Mol, M.; Molina-Porcel, L.; Montrreal, L.; Morelli, L.; Moreno, F.; Morgan, K.; Mosley, T.; Nöthen, M.M.; Muchnik, C.; Mukherjee, S.; Nacmias, B.; Ngandu, T.; Nicolas, G.; Nordestgaard, B.G.; Olaso, R.; Orellana, A.; Orsini, M.; Ortega, G.; Padovani, A.; Paolo, C.; Papenberg, G.; Parnetti, L.; Pasquier, F.; Pastor, P.; Peloso, G.; Pérez-Cordón, A.; Pérez-Tur, J.; Pericard, P.; Peters, O.; Pijnenburg, Y.A.L.; Pineda, J.A.; Piñol-Ripoll, G.; Pisanu, C.; Polak, T.; Popp, J.; Posthuma, D.; Priller, J.; Puerta, R.; Quenez, O.; Quintela, I.; Thomassen, J.Q.; Rábano, A.; Rainero, I.; Rajabli, F.; Ramakers, I.; Real, L.M.; Reinders, M.J.T.; Reitz, C.; Reyes-Dumeyer, D.; Ridge, P.; Riedel-Heller, S.; Riederer, P.; Roberto, N.; Rodriguez-Rodriguez, E.; Rongve, A.; Allende, I.R.; Rosende-Roca, M.; Royo, J.L.; Rubino, E.; Rujescu, D.; Sáez, M.E.; Sakka, P.; Saltvedt, I.; Sanabria, Á.; Sánchez-Arjona, M.B.; Sanchez-Garcia, F.; Juan, P.S.; Sánchez-Valle, R.; Sando, S.B.; Sarnowski, C.; Satizabal, C.L.; Scamosci, M.; Scarmeas, N.; Scarpini, E.; Scheltens, P.; Scherbaum, N.; Scherer, M.; Schmid, M.; Schneider, A.; Schott, J.M.; Selbæk, G.; Seripa, D.; Serrano, M.; Sha, J.; Shadrin, A.A.; Skrobot, O.; Slifer, S.; Snijders, G.J.L.; Soininen, H.; Solfrizzi, V.; Solomon, A.; Song, Y.; Sorbi, S.; Sotolongo-Grau, O.; Spalletta, G.; Spottke, A.; Squassina, A.; Stordal, E.; Tartan, J.P.; Tárraga, L.; Tesí, N.; Thalamuthu, A.; Thomas, T.; Tosto, G.; Traykov, L.; Tremolizzo, L.; Tybjærg-Hansen, A.; Uitterlinden, A.; Ullgren, A.; Ulstein, I.; Valero, S.; Valladares, O.; Broeckhoven, C.V.; Vance, J.; Vardarajan, B.N.; van der Lugt, A.; Dongen, J.V.; van Rooij, J.; van Swieten, J.; Vandenberghe, R.; Verhey, F.; Vidal, J.S.; Vogelgsang, J.; Vyhnalek, M.; Wagner, M.; Wallon, D.; Wang, L.S.; Wang, R.; Weinhold, L.; Wiltfang, J.; Windle, G.; Woods, B.; Yannakoulia, M.; Zare, H.; Zhao, Y.; Zhang, X.; Zhu, C.; Zulaica, M.; Laczo, J.; Matoska, V.; Serpente, M.; Assogna, F.; Piras, F.; Piras, F.; Ciullo, V.; Shofany, J.; Ferrarese, C.; Andreoni, S.; Sala, G.; Zoia, C.P.; Zompo, M.D.; Benussi, A.; Bastiani, P.; Takalo, M.; Natunen, T.; Laatikainen, T.; Tuomilehto, J.; Antikainen, R.; Strandberg, T.; Lindström, J.; Peltonen, M.; Abraham, R.; Al-Chalabi, A.; Bass, N.J.; Brayne, C.; Brown, K.S.; Collinge, J.; Craig, D.; Deloukas, P.; Fox, N.; Gerrish, A.; Gill, M.; Gwilliam, R.; Harold, D.; Hollingworth, P.; Johnston, J.A.; Jones, L.; Lawlor, B.; Livingston, G.; Lovestone, S.; Lupton, M.; Lynch, A.; Mann, D.; McGuinness, B.; McQuillin, A.; O’Donovan, M.C.; Owen, M.J.; Passmore, P.; Powell, J.F.; Proitsi, P.; Rossor, M.; Shaw, C.E.; Smith, A.D.; Gurling, H.; Todd, S.; Mummery, C.; Ryan, N.; Lacidogna, G.; Adarmes-Gómez, A.; Mauleón, A.; Pancho, A.; Gailhajenet, A.; Lafuente, A.; Macias- García, D.; Martín, E.; Pelejà, E.; Carrillo, F.; Merlín, I.S.; Garrote-Espina, L.; Vargas, L.; Carrion-Claro, M.; Marín, M.; Labrador, M.; Buendia, M.; Alonso, M.D.; Guitart, M.; Moreno, M.; Ibarria, M.; Periñán, M.; Aguilera, N.; Gómez-Garre, P.; Cañabate, P.; Escuela, R.; Pineda-Sánchez, R.; Vigo-Ortega, R.; Jesús, S.; Preckler, S.; Rodrigo-Herrero, S.; Diego, S.; Vacca, A.; Roveta, F.; Salvadori, N.; Chipi, E.; Boecker, H.; Laske, C.; Perneczky, R.; Anastasiou, C.; Janowitz, D.; Malik, R.; Anastasiou, A.; Parveen, K.; Lage, C.; López-García, S.; Antonell, A.; Mihova, K.Y.; Belezhanska, D.; Weber, H.; Kochen, S.; Solis, P.; Medel, N.; Lisso, J.; Sevillano, Z.; Politis, D.G.; Cores, V.; Cuesta, C.; Ortiz, C.; Bacha, J.I.; Rios, M.; Saenz, A.; Abalos, M.S.; Kohler, E.; Palacio, D.L.; Etchepareborda, I.; Kohler, M.; Novack, G.; Prestia, F.A.; Galeano, P.; Castaño, E.M.; Germani, S.; Toso, C.R.; Rojo, M.; Ingino, C.; Mangone, C.; Rubinsztein, D.C.; Teipel, S.; Fievet, N.; Deramerourt, V.; Forsell, C.; Thonberg, H.; Bjerke, M.; Roeck, E.D.; Martínez-Larrad, M.T.; Olivar, N.; Aguilera, N.; Cano, A.; Cañabate, P.; Macias, J.; Maroñas, O.; Nuñez-Llaves, R.; Olivé, C.; Pelejá, E.; Adarmes-Gómez, A.D.; Alonso, M.D.; Amer-Ferrer, G.; Antequera, M.; Burguera, J.A.; Carrillo, F.; Carrión-Claro, M.; Casajeros, M.J.; Martinez de Pancorbo, M.; Escuela, R.; Garrote-Espina, L.; Gómez-Garre, P.; Hevilla, S.; Jesús, S.; Espinosa, M.A.L.; Legaz, A.; López-García, S.; Macias-García, D.; Manzanares, S.; Marín, M.; Marín-Muñoz, J.; Marín, T.; Martínez, B.; Martínez, V.; Martínez-Lage Álvarez, P.; Iriarte, M.M.; Periñán-Tocino, M.T.; Pineda-Sánchez, R.; Real de Asúa, D.; Rodrigo, S.; Sastre, I.; Vicente, M.P.; Vigo-Ortega, R.; Vivancos, L.; Epelbaum, J.; Hannequin, D.; campion, D.; Deramecourt, V.; Tzourio, C.; Brice, A.; Dubois, B.; Williams, A.; Thomas, C.; Davies, C.; Nash, W.; Dowzell, K.; Morales, A.C.; Bernardo-Harrington, M.; Turton, J.; Lord, J.; Brown, K.; Vardy, E.; Fisher, E.; Warren, J.D.; Rossor, M.; Ryan, N.S.; Guerreiro, R.; Uphill, J.; Bass, N.; Heun, R.; Kölsch, H.; Schürmann, B.; Lacour, A.; Herold, C.; Johnston, J.A.; Passmore, P.; Powell, J.; Patel, Y.; Hodges, A.; Becker, T.; Warden, D.; Wilcock, G.; Clarke, R.; Deloukas, P.; Ben-Shlomo, Y.; Hooper, N.M.; Pickering-Brown, S.; Sussams, R.; Warner, N.; Bayer, A.; Heuser, I.; Drichel, D.; Klopp, N.; Mayhaus, M.; Riemenschneider, M.; Pinchler, S.; Feulner, T.; Gu, W.; van den Bussche, H.; Hüll, M.; Frölich, L.; Wichmann, H-E.; Jöckel, K-H.; O’Donovan, M.; Owen, M.; Bahrami, S.; Bosnes, I.; Selnes, P.; Bergh, S.; Palotie, A.; Daly, M.; Jacob, H.; Matakidou, A.; Runz, H.; John, S.; Plenge, R.; McCarthy, M.; Hunkapiller, J.; Ehm, M.; Waterworth, D.; Fox, C.; Malarstig, A.; Klinger, K.; Call, K.; Behrens, T.; Loerch, P.; Mäkelä, T.; Kaprio, J.; Virolainen, P.; Pulkki, K.; Kilpi, T.; Perola, M.; Partanen, J.; Pitkäranta, A.; Kaarteenaho, R.; Vainio, S.; Turpeinen, M.; Serpi, R.; Laitinen, T.; Mäkelä, J.; Kosma, V-M.; Kujala, U.; Tuovila, O.; Hendolin, M.; Pakkanen, R.; Waring, J.; Riley-Gillis, B.; Liu, J.; Biswas, S.; Diogo, D.; Marshall, C.; Hu, X.; Gossel, M.; Graham, R.; Cummings, B.; Ripatti, S.; Schleutker, J.; Arvas, M.; Carpén, O.; Hinttala, R.; Kettunen, J.; Mannermaa, A.; Laukkanen, J.; Julkunen, V.; Remes, A.; Kälviäinen, R.; Peltola, J.; Tienari, P.; Rinne, J.; Ziemann, A.; Waring, J.; Esmaeeli, S.; Smaoui, N.; Lehtonen, A.; Eaton, S.; Lahdenperä, S.; van Adelsberg, J.; Michon, J.; Kerchner, G.; Bowers, N.; Teng, E.; Eicher, J.; Mehta, V.; Gormley, P.; Linden, K.; Whelan, C.; Xu, F.; Pulford, D.; Färkkilä, M.; Pikkarainen, S.; Jussila, A.; Blomster, T.; Kiviniemi, M.; Voutilainen, M.; Georgantas, B.; Heap, G.; Rahimov, F.; Usiskin, K.; Lu, T.; Oh, D.; Kalpala, K.; Miller, M.; McCarthy, L.; Eklund, K.; Palomäki, A.; Isomäki, P.; Pirilä, L.; Kaipiainen-Seppänen, O.; Huhtakangas, J.; Lertratanakul, A.; Hochfeld, M.; Bing, N.; Gordillo, J.E.; Mars, N.; Pelkonen, M.; Kauppi, P.; Kankaanranta, H.; Harju, T.; Close, D.; Greenberg, S.; Chen, H.; Betts, J.; Ghosh, S.; Salomaa, V.; Niiranen, T.; Juonala, M.; Metsärinne, K.; Kähönen, M.; Junttila, J.; Laakso, M.; Pihlajamäki, J.; Sinisalo, J.; Taskinen, M-R.; Tuomi, T.; Challis, B.; Peterson, A.; Chu, A.; Parkkinen, J.; Muslin, A.; Joensuu, H.; Meretoja, T.; Aaltonen, L.; Mattson, J.; Auranen, A.; Karihtala, P.; Kauppila, S.; Auvinen, P.; Elenius, K.; Popovic, R.; Schutzman, J.; Loboda, A.; Chhibber, A.; Lehtonen, H.; McDonough, S.; Crohns, M.; Kulkarni, D.; Kaarniranta, K.; Turunen, J.A.; Ollila, T.; Seitsonen, S.; Uusitalo, H.; Aaltonen, V.; Uusitalo-Järvinen, H.; Luodonpää, M.; Hautala, N.; Loomis, S.; Strauss, E.; Chen, H.; Podgornaia, A.; Hoffman, J.; Tasanen, K.; Huilaja, L.; Hannula-Jouppi, K.; Salmi, T.; Peltonen, S.; Koulu, L.; Harvima, I.; Wu, Y.; Choy, D.; Pussinen, P.; Salminen, A.; Salo, T.; Rice, D.; Nieminen, P.; Palotie, U.; Siponen, M.; Suominen, L.; Mäntylä, P.; Gursoy, U.; Anttonen, V.; Sipilä, K.; Davis, J.W.; Quarless, D.; Petrovski, S.; Wigmore, E.; Chen, C-Y.; Bronson, P.; Tsai, E.; Huang, Y.; Maranville, J.; Shaikho, E.; Mohammed, E.; Wadhawan, S.; Kvikstad, E.; Caliskan, M.; Chang, D.; Bhangale, T.; Pendergrass, S.; Holzinger, E.; Chen, X.; Hedman, Å.; King, K.S.; Wang, C.; Xu, E.; Auge, F.; Chatelain, C.; Rajpal, D.; Liu, D.; Call, K.; Xia, T.; Brauer, M.; Kurki, M.; Karjalainen, J.; Havulinna, A.; Jalanko, A.; Palta, P.; della Briotta Parolo, P.; Zhou, W.; Lemmelä, S.; Rivas, M.; Harju, J.; Lehisto, A.; Ganna, A.; Llorens, V.; Laivuori, H.; Rüeger, S.; Niemi, M.E.; Tukiainen, T.; Reeve, M.P.; Heyne, H.; Palin, K.; Garcia-Tabuenca, J.; Siirtola, H.; Kiiskinen, T.; Lee, J.; Tsuo, K.; Elliott, A.; Kristiansson, K.; Hyvärinen, K.; Ritari, J.; Koskinen, M.; Pylkäs, K.; Kalaoja, M.; Karjalainen, M.; Mantere, T.; Kangasniemi, E.; Heikkinen, S.; Laakkonen, E.; Sipeky, C.; Heron, S.; Karlsson, A.; Jambulingam, D.; Rathinakannan, V.S.; Kajanne, R.; Aavikko, M.; Jiménez, M.G.; della Briotta Parola, P.; Lehistö, A.; Kanai, M.; Kaunisto, M.; Kilpeläinen, E.; Sipilä, T.P.; Brein, G.; Awaisa, G.; Shcherban, A.; Donner, K.; Loukola, A.; Laiho, P.; Sistonen, T.; Kaiharju, E.; Laukkanen, M.; Järvensivu, E.; Lähteenmäki, S.; Männikkö, L.; Wong, R.; Mattsson, H.; Hiekkalinna, T.; Paajanen, T.; Pärn, K.; Gracia-Tabuenca, J.; Abner, E.; Adams, P.M.; Aguirre, A.; Albert, M.S.; Albin, R.L.; Allen, M.; Alvarez, L.; Apostolova, L.G.; Arnold, S.E.; Asthana, S.; Atwood, C.S.; Ayres, G.; Baldwin, C.T.; Barber, R.C.; Barnes, L.L.; Barral, S.; Beach, T.G.; Becker, J.T.; Beecham, G.W.; Beekly, D.; Below, J.E.; Benchek, P.; Benitez, B.A.; Bennett, D.; Bertelson, J.; Margaret, F.E.; Bird, T.D.; Blacker, D.; Boeve, B.F.; Bowen, J.D.; Boxer, A.; Brewer, J.; Burke, J.R.; Burns, J.M.; Bush, W.S.; Buxbaum, J.D.; Cairns, N.J.; Cao, C.; Carlson, C.S.; Carlsson, C.M.; Carney, R.M.; Carrasquillo, M.M.; Chasse, S.; Chesselet, M-F.; Chesi, A.; Chin, N.A.; Chui, H.C.; Chung, J.; Craft, S.; Crane, P.K.; Cribbs, D.H.; Crocco, E.A.; Cruchaga, C.; Cuccaro, M.L.; Cullum, M.; Darby, E.; Davis, B.; De Jager, P.L.; DeCarli, C.; DeToledo, J.; Dick, M.; Dickson, D.W.; Dombroski, B.A.; Doody, R.S.; Duara, R.; Ertekin-Taner, N.; Evans, D.A.; Fairchild, T.J.; Fallon, K.B.; Farlow, M.R.; Farrell, J.J.; Fernandez-Hernandez, V.; Ferris, S.; Frosch, M.P.; Fulton-Howard, B.; Galasko, D.R.; Gamboa, A.; Gearing, M.; Geschwind, D.H.; Ghetti, B.; Gilbert, J.R.; Grabowski, T.J.; Graff-Radford, N.R.; Grant, S.F.A.; Green, R.C.; Growdon, J.H.; Haines, J.L.; Hakonarson, H.; Hall, J.; Hamilton, R.L.; Harari, O.; Harrell, L.E.; Haut, J.; Head, E.; Henderson, V.W.; Hernandez, M.; Hohman, T.; Honig, L.S.; Huebinger, R.M.; Huentelman, M.J.; Hulette, C.M.; Hyman, B.T.; Hynan, L.S.; Ibanez, L.; Jarvik, G.P.; Jayadev, S.; Jin, L-W.; Johnson, K.; Johnson, L.; Kamboh, M.I.; Karydas, A.M.; Katz, M.J.; Kaye, J.A.; Keene, C.D.; Khaleeq, A.; Kim, R.; Knebl, J.; Kowall, N.W.; Kramer, J.H.; Kuksa, P.P.; LaFerla, F.M.; Lah, J.J.; Larson, E.B.; Lee, C-Y.; Lee, E.B.; Lerner, A.; Leung, Y.Y.; Leverenz, J.B.; Levey, A.I.; Li, M.; Lieberman, A.P.; Lipton, R.B.; Logue, M.; Lyketsos, C.G.; Malamon, J.; Mains, D.; Marson, D.C.; Martiniuk, F.; Mash, D.C.; Masliah, E.; Massman, P.; Masurkar, A.; McCormick, W.C.; McCurry, S.M.; McDavid, A.N.; McDonough, S.; McKee, A.C.; Mesulam, M.; Mez, J.; Miller, B.L.; Miller, C.A.; Miller, J.W.; Montine, T.J.; Monuki, E.S.; Morris, J.C.; Myers, A.J.; Nguyen, T.; O’Bryant, S.; Olichney, J.M.; Ory, M.; Palmer, R.; Parisi, J.E.; Paulson, H.L.; Pavlik, V.; Paydarfar, D.; Perez, V.; Peskind, E.; Petersen, R.C.; Phillips-Cremins, J.E.; Pierce, A.; Polk, M.; Poon, W.W.; Potter, H.; Qu, L.; Quiceno, M.; Quinn, J.F.; Raj, A.; Raskind, M.; Reiman, E.M.; Reisberg, B.; Reisch, J.S.; Ringman, J.M.; Roberson, E.D.; Rodriguear, M.; Rogaeva, E.; Rosen, H.J.; Rosenberg, R.N.; Royall, D.R.; Sager, M.A.; Sano, M.; Saykin, A.J.; Schneider, J.A.; Schneider, L.S.; Seeley, W.W.; Slifer, S.H.; Small, S.; Smith, A.G.; Smith, J.P.; Song, Y.E.; Sonnen, J.A.; Spina, S.; George-Hyslop, P.S.; Stern, R.A.; Stevens, A.B.; Strittmatter, S.M.; Sultzer, D.; Swerdlow, R.H.; Tanzi, R.E.; Tilson, J.L.; Trojanowski, J.Q.; Troncoso, J.C.; Tsuang, D.W.; Valladares, O.; Van Deerlin, V.M.; van Eldik, L.J.; Vassar, R.; Vinters, H.V.; Vonsattel, J-P.; Weintraub, S.; Welsh-Bohmer, K.A.; Whitehead, P.L.; Wijsman, E.M.; Wilhelmsen, K.C.; Williams, B.; Williamson, J.; Wilms, H.; Wingo, T.S.; Wisniewski, T.; Woltjer, R.L.; Woon, M.; Wright, C.B.; Wu, C-K.; Younkin, S.G.; Yu, C-E.; Yu, L.; Zhang, Y.; Zhao, Y.; Zhu, X.; Adams, H.; Akinyemi, R.O.; Ali, M.; Armstrong, N.; Aparicio, H.J.; Bahadori, M.; Becker, J.T.; Breteler, M.; Chasman, D.; Chauhan, G.; Comic, H.; Cox, S.; Cupples, A.L.; Davies, G.; DeCarli, C.S.; Duperron, M-G.; Dupuis, J.; Evans, T.; Fan, F.; Fitzpatrick, A.; Fohner, A.E.; Ganguli, M.; Geerlings, M.; Glatt, S.J.; Gonzalez, H.M.; Goss, M.; Grabe, H.; Habes, M.; Heckbert, S.R.; Hofer, E.; Hong, E.; Hughes, T.; Kautz, T.F.; Knol, M.; Kremen, W.; Lacaze, P.; Lahti, J.; Grand, Q.L.; Litkowski, E.; Li, S.; Liu, D.; Liu, X.; Loitfelder, M.; Manning, A.; Maillard, P.; Marioni, R.; Mazoyer, B.; van Lent, D.M.; Mei, H.; Mishra, A.; Nyquist, P.; O’Connell, J.; Patel, Y.; Paus, T.; Pausova, Z.; Raikkonen-Talvitie, K.; Riaz, M.; Rich, S.; Rotter, J.; Romero, J.; Roshchupkin, G.; Saba, Y.; Sargurupremraj, M.; Schmidt, H.; Schmidt, R.; Shulman, J.M.; Smith, J.; Sekhar, H.; Rajula, R.; Shin, J.; Simino, J.; Sliz, E.; Teumer, A.; Thomas, A.; Tin, A.; Tucker-Drob, E.; Vojinovic, D.; Wang, Y.; Weinstein, G.; Williams, D.; Wittfeld, K.; Yanek, L.; Yang, Y.; Farrer, L.A.; Psaty, B.M.; Ghanbari, M.; Raj, T.; Sachdev, P.; Mather, K.; Jessen, F.; Ikram, M.A.; de Mendonça, A.; Hort, J.; Tsolaki, M.; Pericak-Vance, M.A.; Amouyel, P.; Williams, J.; Frikke-Schmidt, R.; Clarimon, J.; Deleuze, J-F.; Rossi, G.; Seshadri, S.; Andreassen, O.A.; Ingelsson, M.; Hiltunen, M.; Sleegers, K.; Schellenberg, G.D.; van Duijn, C.M.; Sims, R.; van der Flier, W.M.; Ruiz, A.; Ramirez, A.; Lambert, J-C. New insights into the genetic etiology of Alzheimer’s disease and related dementias. Nat. Genet., 2022, 54(4), 412-436.
[http://dx.doi.org/10.1038/s41588-022-01024-z] [PMID: 35379992]
[6]
Tan, M.S.; Jiang, T.; Tan, L.; Yu, J.T. Genome-wide association studies in neurology. Ann. Transl. Med., 2014, 2(12), 124.
[http://dx.doi.org/10.3978/j.issn.2305-5839.2014.11.12] [PMID: 25568877]
[7]
Sasaki, H.; Nagura, K.; Ishino, M.; Tobioka, H.; Kotani, K.; Sasaki, T. Cloning and characterization of cell adhesion kinase beta, a novel protein-tyrosine kinase of the focal adhesion kinase subfamily. J. Biol. Chem., 1995, 270(36), 21206-21219.
[http://dx.doi.org/10.1074/jbc.270.36.21206] [PMID: 7673154]
[8]
Herzog, H.; Nicholl, J.; Hort, Y.J.; Sutherland, G.R.; Shine, J. Molecular cloning and assignment of FAK2, a novel human focal adhesion kinase, to 8p11.2-p22 by nonisotopic in situ hybridization. Genomics, 1996, 32(3), 484-486.
[http://dx.doi.org/10.1006/geno.1996.0149] [PMID: 8838818]
[9]
Yu, H.; Li, X.; Marchetto, G.S.; Dy, R.; Hunter, D.; Calvo, B.; Dawson, T.L.; Wilm, M.; Anderegg, R.J.; Graves, L.M.; Earp, H.S. Activation of a novel calcium-dependent protein-tyrosine kinase. Correlation with c-Jun N-terminal kinase but not mitogen-activated protein kinase activation. J. Biol. Chem., 1996, 271(47), 29993-29998.
[http://dx.doi.org/10.1074/jbc.271.47.29993] [PMID: 8939945]
[10]
Avraham, S.; London, R.; Fu, Y.; Ota, S.; Hiregowdara, D.; Li, J.; Jiang, S.; Pasztor, L.M.; White, R.A.; Groopman, J.E.; Avraham, H. Identification and characterization of a novel related adhesion focal tyrosine kinase (RAFTK) from megakaryocytes and brain. J. Biol. Chem., 1995, 270(46), 27742-27751.
[http://dx.doi.org/10.1074/jbc.270.46.27742] [PMID: 7499242]
[11]
Lambert, J.C.; Ibrahim-Verbaas, C.A.; Harold, D.; Naj, A.C.; Sims, R.; Bellenguez, C.; Jun, G.; DeStefano, A.L.; Bis, J.C.; Beecham, G.W.; Grenier-Boley, B.; Russo, G.; Thornton-Wells, T.A.; Jones, N.; Smith, A.V.; Chouraki, V.; Thomas, C.; Ikram, M.A.; Zelenika, D.; Vardarajan, B.N.; Kamatani, Y.; Lin, C-F.; Gerrish, A.; Schmidt, H.; Kunkle, B.; Dunstan, M.L.; Ruiz, A.; Bihoreau, M-T.; Choi, S-H.; Reitz, C.; Pasquier, F.; Hollingworth, P.; Ramirez, A.; Hanon, O.; Fitzpatrick, A.L.; Buxbaum, J.D.; Campion, D.; Crane, P.K.; Baldwin, C.; Becker, T.; Gudnason, V.; Cruchaga, C.; Craig, D.; Amin, N.; Berr, C.; Lopez, O.L.; De Jager, P.L.; Deramecourt, V.; Johnston, J.A.; Evans, D.; Lovestone, S.; Letenneur, L.; Morón, F.J.; Rubinsztein, D.C.; Eiriksdottir, G.; Sleegers, K.; Goate, A.M.; Fiévet, N.; Huentelman, M.J.; Gill, M.; Brown, K.; Kamboh, M.I.; Keller, L.; Barberger-Gateau, P.; McGuinness, B.; Larson, E.B.; Green, R.; Myers, A.J.; Dufouil, C.; Todd, S.; Wallon, D.; Love, S.; Rogaeva, E.; Gallacher, J.; St George-Hyslop, P.; Clarimon, J.; Lleo, A.; Bayer, A.; Tsuang, D.W.; Yu, L.; Tsolaki, M.; Bossù, P.; Spalletta, G.; Proitsi, P.; Collinge, J.; Sorbi, S.; Sanchez-Garcia, F.; Fox, N.C.; Hardy, J.; Naranjo, M.C.D.; Bosco, P.; Clarke, R.; Brayne, C.; Galimberti, D.; Mancuso, M.; Matthews, F.; Moebus, S.; Mecocci, P.; Del Zompo, M.; Maier, W.; Hampel, H.; Pilotto, A.; Bullido, M.; Panza, F.; Caffarra, P.; Nacmias, B.; Gilbert, J.R.; Mayhaus, M.; Lannfelt, L.; Hakonarson, H.; Pichler, S.; Carrasquillo, M.M.; Ingelsson, M.; Beekly, D.; Alvarez, V.; Zou, F.; Valladares, O.; Younkin, S.G.; Coto, E.; Hamilton-Nelson, K.L.; Gu, W.; Razquin, C.; Pastor, P.; Mateo, I.; Owen, M.J.; Faber, K.M.; Jonsson, P.V.; Combarros, O.; O’Donovan, M.C.; Cantwell, L.B.; Soininen, H.; Blacker, D.; Mead, S.; Mosley, T.H., Jr; Bennett, D.A.; Harris, T.B.; Fratiglioni, L.; Holmes, C.; de Bruijn, R.F.A.G.; Passmore, P.; Montine, T.J.; Bettens, K.; Rotter, J.I.; Brice, A.; Morgan, K.; Foroud, T.M.; Kukull, W.A.; Hannequin, D.; Powell, J.F.; Nalls, M.A.; Ritchie, K.; Lunetta, K.L.; Kauwe, J.S.K.; Boerwinkle, E.; Riemenschneider, M.; Boada, M.; Hiltunen, M.; Martin, E.R.; Schmidt, R.; Rujescu, D.; Wang, L-S.; Dartigues, J-F.; Mayeux, R.; Tzourio, C.; Hofman, A.; Nöthen, M.M.; Graff, C.; Psaty, B.M.; Jones, L.; Haines, J.L.; Holmans, P.A.; Lathrop, M.; Pericak-Vance, M.A.; Launer, L.J.; Farrer, L.A.; van Duijn, C.M.; Van Broeckhoven, C.; Moskvina, V.; Seshadri, S.; Williams, J.; Schellenberg, G.D.; Amouyel, P. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat. Genet., 2013, 45(12), 1452-1458.
[http://dx.doi.org/10.1038/ng.2802] [PMID: 24162737]
[12]
Kunkle, B.W.; Grenier-Boley, B.; Sims, R.; Bis, J.C.; Damotte, V.; Naj, A.C.; Boland, A.; Vronskaya, M.; van der Lee, S.J.; Amlie-Wolf, A.; Bellenguez, C.; Frizatti, A.; Chouraki, V.; Martin, E.R.; Sleegers, K.; Badarinarayan, N.; Jakobsdottir, J.; Hamilton-Nelson, K.L.; Moreno-Grau, S.; Olaso, R.; Raybould, R.; Chen, Y.; Kuzma, A.B.; Hiltunen, M.; Morgan, T.; Ahmad, S.; Vardarajan, B.N.; Epelbaum, J.; Hoffmann, P.; Boada, M.; Beecham, G.W.; Garnier, J.G.; Harold, D.; Fitzpatrick, A.L.; Valladares, O.; Moutet, M.L.; Gerrish, A.; Smith, A.V.; Qu, L.; Bacq, D.; Denning, N.; Jian, X.; Zhao, Y.; Del Zompo, M.; Fox, N.C.; Choi, S.H.; Mateo, I.; Hughes, J.T.; Adams, H.H.; Malamon, J.; Sanchez-Garcia, F.; Patel, Y.; Brody, J.A.; Dombroski, B.A.; Naranjo, M.C.D.; Daniilidou, M.; Eiriksdottir, G.; Mukherjee, S.; Wallon, D.; Uphill, J.; Aspelund, T.; Cantwell, L.B.; Garzia, F.; Galimberti, D.; Hofer, E.; Butkiewicz, M.; Fin, B.; Scarpini, E.; Sarnowski, C.; Bush, W.S.; Meslage, S.; Kornhuber, J.; White, C.C.; Song, Y.; Barber, R.C.; Engelborghs, S.; Sordon, S.; Voijnovic, D.; Adams, P.M.; Vandenberghe, R.; Mayhaus, M.; Cupples, L.A.; Albert, M.S.; De Deyn, P.P.; Gu, W.; Himali, J.J.; Beekly, D.; Squassina, A.; Hartmann, A.M.; Orellana, A.; Blacker, D.; Rodriguez-Rodriguez, E.; Lovestone, S.; Garcia, M.E.; Doody, R.S.; Munoz-Fernadez, C.; Sussams, R.; Lin, H.; Fairchild, T.J.; Benito, Y.A.; Holmes, C.; Karamujić-Čomić, H.; Frosch, M.P.; Thonberg, H.; Maier, W.; Roshchupkin, G.; Ghetti, B.; Giedraitis, V.; Kawalia, A.; Li, S.; Huebinger, R.M.; Kilander, L.; Moebus, S.; Hernández, I.; Kamboh, M.I.; Brundin, R.; Turton, J.; Yang, Q.; Katz, M.J.; Concari, L.; Lord, J.; Beiser, A.S.; Keene, C.D.; Helisalmi, S.; Kloszewska, I.; Kukull, W.A.; Koivisto, A.M.; Lynch, A.; Tarraga, L.; Larson, E.B.; Haapasalo, A.; Lawlor, B.; Mosley, T.H.; Lipton, R.B.; Solfrizzi, V.; Gill, M.; Longstreth, W.T., Jr; Montine, T.J.; Frisardi, V.; Diez-Fairen, M.; Rivadeneira, F.; Petersen, R.C.; Deramecourt, V.; Alvarez, I.; Salani, F.; Ciaramella, A.; Boerwinkle, E.; Reiman, E.M.; Fievet, N.; Rotter, J.I.; Reisch, J.S.; Hanon, O.; Cupidi, C.; Andre Uitterlinden, A.G.; Royall, D.R.; Dufouil, C.; Maletta, R.G.; de Rojas, I.; Sano, M.; Brice, A.; Cecchetti, R.; George-Hyslop, P.S.; Ritchie, K.; Tsolaki, M.; Tsuang, D.W.; Dubois, B.; Craig, D.; Wu, C.K.; Soininen, H.; Avramidou, D.; Albin, R.L.; Fratiglioni, L.; Germanou, A.; Apostolova, L.G.; Keller, L.; Koutroumani, M.; Arnold, S.E.; Panza, F.; Gkatzima, O.; Asthana, S.; Hannequin, D.; Whitehead, P.; Atwood, C.S.; Caffarra, P.; Hampel, H.; Quintela, I.; Carracedo, Á.; Lannfelt, L.; Rubinsztein, D.C.; Barnes, L.L.; Pasquier, F.; Frölich, L.; Barral, S.; McGuinness, B.; Beach, T.G.; Johnston, J.A.; Becker, J.T.; Passmore, P.; Bigio, E.H.; Schott, J.M.; Bird, T.D.; Warren, J.D.; Boeve, B.F.; Lupton, M.K.; Bowen, J.D.; Proitsi, P.; Boxer, A.; Powell, J.F.; Burke, J.R.; Kauwe, J.S.K.; Burns, J.M.; Mancuso, M.; Buxbaum, J.D.; Bonuccelli, U.; Cairns, N.J.; McQuillin, A.; Cao, C.; Livingston, G.; Carlson, C.S.; Bass, N.J.; Carlsson, C.M.; Hardy, J.; Carney, R.M.; Bras, J.; Carrasquillo, M.M.; Guerreiro, R.; Allen, M.; Chui, H.C.; Fisher, E.; Masullo, C.; Crocco, E.A.; DeCarli, C.; Bisceglio, G.; Dick, M.; Ma, L.; Duara, R.; Graff-Radford, N.R.; Evans, D.A.; Hodges, A.; Faber, K.M.; Scherer, M.; Fallon, K.B.; Riemenschneider, M.; Fardo, D.W.; Heun, R.; Farlow, M.R.; Kölsch, H.; Ferris, S.; Leber, M.; Foroud, T.M.; Heuser, I.; Galasko, D.R.; Giegling, I.; Gearing, M.; Hüll, M.; Geschwind, D.H.; Gilbert, J.R.; Morris, J.; Green, R.C.; Mayo, K.; Growdon, J.H.; Feulner, T.; Hamilton, R.L.; Harrell, L.E.; Drichel, D.; Honig, L.S.; Cushion, T.D.; Huentelman, M.J.; Hollingworth, P.; Hulette, C.M.; Hyman, B.T.; Marshall, R.; Jarvik, G.P.; Meggy, A.; Abner, E.; Menzies, G.E.; Jin, L.W.; Leonenko, G.; Real, L.M.; Jun, G.R.; Baldwin, C.T.; Grozeva, D.; Karydas, A.; Russo, G.; Kaye, J.A.; Kim, R.; Jessen, F.; Kowall, N.W.; Vellas, B.; Kramer, J.H.; Vardy, E.; LaFerla, F.M.; Jöckel, K.H.; Lah, J.J.; Dichgans, M.; Leverenz, J.B.; Mann, D.; Levey, A.I.; Pickering-Brown, S.; Lieberman, A.P.; Klopp, N.; Lunetta, K.L.; Wichmann, H.E.; Lyketsos, C.G.; Morgan, K.; Marson, D.C.; Brown, K.; Martiniuk, F.; Medway, C.; Mash, D.C.; Nöthen, M.M.; Masliah, E.; Hooper, N.M.; McCormick, W.C.; Daniele, A.; McCurry, S.M.; Bayer, A.; McDavid, A.N.; Gallacher, J.; McKee, A.C.; van den Bussche, H.; Mesulam, M.; Brayne, C.; Miller, B.L.; Riedel-Heller, S.; Miller, C.A.; Miller, J.W.; Al-Chalabi, A.; Morris, J.C.; Shaw, C.E.; Myers, A.J.; Wiltfang, J.; O’Bryant, S.; Olichney, J.M.; Alvarez, V.; Parisi, J.E.; Singleton, A.B.; Paulson, H.L.; Collinge, J.; Perry, W.R.; Mead, S.; Peskind, E.; Cribbs, D.H.; Rossor, M.; Pierce, A.; Ryan, N.S.; Poon, W.W.; Nacmias, B.; Potter, H.; Sorbi, S.; Quinn, J.F.; Sacchinelli, E.; Raj, A.; Spalletta, G.; Raskind, M.; Caltagirone, C.; Bossù, P.; Orfei, M.D.; Reisberg, B.; Clarke, R.; Reitz, C.; Smith, A.D.; Ringman, J.M.; Warden, D.; Roberson, E.D.; Wilcock, G.; Rogaeva, E.; Bruni, A.C.; Rosen, H.J.; Gallo, M.; Rosenberg, R.N.; Ben-Shlomo, Y.; Sager, M.A.; Mecocci, P.; Saykin, A.J.; Pastor, P.; Cuccaro, M.L.; Vance, J.M.; Schneider, J.A.; Schneider, L.S.; Slifer, S.; Seeley, W.W.; Smith, A.G.; Sonnen, J.A.; Spina, S.; Stern, R.A.; Swerdlow, R.H.; Tang, M.; Tanzi, R.E.; Trojanowski, J.Q.; Troncoso, J.C.; Van Deerlin, V.M.; Van Eldik, L.J.; Vinters, H.V.; Vonsattel, J.P.; Weintraub, S.; Welsh-Bohmer, K.A.; Wilhelmsen, K.C.; Williamson, J.; Wingo, T.S.; Woltjer, R.L.; Wright, C.B.; Yu, C.E.; Yu, L.; Saba, Y.; Pilotto, A.; Bullido, M.J.; Peters, O.; Crane, P.K.; Bennett, D.; Bosco, P.; Coto, E.; Boccardi, V.; De Jager, P.L.; Lleo, A.; Warner, N.; Lopez, O.L.; Ingelsson, M.; Deloukas, P.; Cruchaga, C.; Graff, C.; Gwilliam, R.; Fornage, M.; Goate, A.M.; Sanchez-Juan, P.; Kehoe, P.G.; Amin, N.; Ertekin-Taner, N.; Berr, C.; Debette, S.; Love, S.; Launer, L.J.; Younkin, S.G.; Dartigues, J.F.; Corcoran, C.; Ikram, M.A.; Dickson, D.W.; Nicolas, G.; Campion, D.; Tschanz, J.; Schmidt, H.; Hakonarson, H.; Clarimon, J.; Munger, R.; Schmidt, R.; Farrer, L.A.; Van Broeckhoven, C.; C O’Donovan, M.; DeStefano, A.L.; Jones, L.; Haines, J.L.; Deleuze, J.F.; Owen, M.J.; Gudnason, V.; Mayeux, R.; Escott-Price, V.; Psaty, B.M.; Ramirez, A.; Wang, L.S.; Ruiz, A.; van Duijn, C.M.; Holmans, P.A.; Seshadri, S.; Williams, J.; Amouyel, P.; Schellenberg, G.D.; Lambert, J.C.; Pericak-Vance, M.A. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Nat. Genet., 2019, 51(3), 414-430.
[http://dx.doi.org/10.1038/s41588-019-0358-2] [PMID: 30820047]
[13]
Schwartzentruber, J.; Cooper, S.; Liu, J.Z.; Barrio-Hernandez, I.; Bello, E.; Kumasaka, N.; Young, A.M.H.; Franklin, R.J.M.; Johnson, T.; Estrada, K.; Gaffney, D.J.; Beltrao, P.; Bassett, A. Genome-wide meta-analysis, fine-mapping and integrative prioritization implicate new Alzheimer’s disease risk genes. Nat. Genet., 2021, 53(3), 392-402.
[http://dx.doi.org/10.1038/s41588-020-00776-w] [PMID: 33589840]
[14]
Sierksma, A.; Escott-Price, V.; De Strooper, B. Translating genetic risk of Alzheimer’s disease into mechanistic insight and drug targets. Science, 2020, 370(6512), 61-66.
[http://dx.doi.org/10.1126/science.abb8575] [PMID: 33004512]
[15]
Tripathi, P.N.; Srivastava, P.; Sharma, P.; Tripathi, M.K.; Seth, A.; Tripathi, A.; Rai, S.N.; Singh, S.P.; Shrivastava, S.K. Biphenyl-3-oxo-1,2,4-triazine linked piperazine derivatives as potential cholinesterase inhibitors with anti-oxidant property to improve the learning and memory. Bioorg. Chem., 2019, 85, 82-96.
[http://dx.doi.org/10.1016/j.bioorg.2018.12.017] [PMID: 30605887]
[16]
Srivastava, P.; Tripathi, P.N.; Sharma, P.; Rai, S.N.; Singh, S.P.; Srivastava, R.K.; Shankar, S.; Shrivastava, S.K. Design and development of some phenyl benzoxazole derivatives as a potent acetylcholinesterase inhibitor with antioxidant property to enhance learning and memory. Eur. J. Med. Chem., 2019, 163, 116-135.
[http://dx.doi.org/10.1016/j.ejmech.2018.11.049] [PMID: 30503937]
[17]
Rai, S.N.; Zahra, W.; Birla, H.; Singh, S.S.; Singh, S.P. Commentary: Mild endoplasmic reticulum stress ameliorates lpopolysaccharide-induced neuroinflammation and cognitive impairment via regulation of microglial polarization. Front. Aging Neurosci., 2018, 10, 192.
[http://dx.doi.org/10.3389/fnagi.2018.00192] [PMID: 29988480]
[18]
Ramakrishna, K.; Nalla, L.V.; Naresh, D.; Venkateswarlu, K.; Viswanadh, M.K.; Nalluri, B.N.; Chakravarthy, G.; Duguluri, S.; Singh, P.; Rai, S.N.; Kumar, A.; Singh, V.; Singh, S.K. WNT-β Catenin signaling as a potential therapeutic target for neurodegenerative diseases: Current status and future perspective. Diseases, 2023, 11(3), 89.
[http://dx.doi.org/10.3390/diseases11030089] [PMID: 37489441]
[19]
Giralt, A.; de Pins, B.; Cifuentes-Díaz, C.; López-Molina, L.; Farah, A.T.; Tible, M.; Deramecourt, V.; Arold, S.T.; Ginés, S.; Hugon, J.; Girault, J.A. PTK2B/Pyk2 overexpression improves a mouse model of Alzheimer’s disease. Exp. Neurol., 2018, 307, 62-73.
[http://dx.doi.org/10.1016/j.expneurol.2018.05.020] [PMID: 29803828]
[20]
de Pins, B.; Mendes, T.; Giralt, A.; Girault, J.A. The non-receptor tyrosine kinase Pyk2 in brain function and neurological and psychiatric diseases. Front. Synaptic Neurosci., 2021, 13, 749001.
[http://dx.doi.org/10.3389/fnsyn.2021.749001] [PMID: 34690733]
[21]
Brody, A.H.; Nies, S.H.; Guan, F.; Smith, L.M.; Mukherjee, B.; Salazar, S.A.; Lee, S.; Lam, T.K.T.; Strittmatter, S.M. Alzheimer risk gene product Pyk2 suppresses tau phosphorylation and phenotypic effects of tauopathy. Mol. Neurodegener., 2022, 17(1), 32.
[http://dx.doi.org/10.1186/s13024-022-00526-y] [PMID: 35501917]
[22]
López-Molina, L.; Fernández-Irigoyen, J.; Cifuentes-Díaz, C.; Alberch, J.; Girault, J.A.; Santamaría, E.; Ginés, S.; Giralt, A. Pyk2 regulates MAMs and mitochondrial dynamics in hippocampal neurons. Cells, 2022, 11(5), 842.
[http://dx.doi.org/10.3390/cells11050842] [PMID: 35269464]
[23]
Mhatre, S.D.; Tsai, C.A.; Rubin, A.J.; James, M.L.; Andreasson, K.I. Microglial malfunction: The third rail in the development of Alzheimer’s disease. Trends Neurosci., 2015, 38(10), 621-636.
[http://dx.doi.org/10.1016/j.tins.2015.08.006] [PMID: 26442696]
[24]
Grubman, A.; Chew, G.; Ouyang, J.F.; Sun, G.; Choo, X.Y.; McLean, C.; Simmons, R.K.; Buckberry, S.; Vargas-Landin, D.B.; Poppe, D.; Pflueger, J.; Lister, R.; Rackham, O.J.L.; Petretto, E.; Polo, J.M. A single-cell atlas of entorhinal cortex from individuals with Alzheimer’s disease reveals cell-type-specific gene expression regulation. Nat. Neurosci., 2019, 22(12), 2087-2097.
[http://dx.doi.org/10.1038/s41593-019-0539-4] [PMID: 31768052]
[25]
Young, A.M.H.; Kumasaka, N.; Calvert, F.; Hammond, T.R.; Knights, A.; Panousis, N.; Park, J.S.; Schwartzentruber, J.; Liu, J.; Kundu, K.; Segel, M.; Murphy, N.A.; McMurran, C.E.; Bulstrode, H.; Correia, J.; Budohoski, K.P.; Joannides, A.; Guilfoyle, M.R.; Trivedi, R.; Kirollos, R.; Morris, R.; Garnett, M.R.; Timofeev, I.; Jalloh, I.; Holland, K.; Mannion, R.; Mair, R.; Watts, C.; Price, S.J.; Kirkpatrick, P.J.; Santarius, T.; Mountjoy, E.; Ghoussaini, M.; Soranzo, N.; Bayraktar, O.A.; Stevens, B.; Hutchinson, P.J.; Franklin, R.J.M.; Gaffney, D.J. A map of transcriptional heterogeneity and regulatory variation in human microglia. Nat. Genet., 2021, 53(6), 861-868.
[http://dx.doi.org/10.1038/s41588-021-00875-2] [PMID: 34083789]
[26]
Sakae, N.; Heckman, M.G.; Vargas, E.R.; Carrasquillo, M.M.; Murray, M.E.; Kasanuki, K.; Ertekin-Taner, N.; Younkin, S.G.; Dickson, D.W. Evaluation of associations of alzheimer’s disease risk variants that are highly expressed in microglia with neuropathological outcome measures. J. Alzheimers Dis., 2019, 70(3), 659-666.
[http://dx.doi.org/10.3233/JAD-190451] [PMID: 31256143]
[27]
Hanks, S.K.; Polte, T.R. Signaling through focal adhesion kinase. BioEssays, 1997, 19(2), 137-145.
[http://dx.doi.org/10.1002/bies.950190208] [PMID: 9046243]
[28]
Orr, A.W.; Murphy-Ullrich, J.E. Regulation of endothelial cell function BY FAK and PYK2. Front. Biosci., 2004, 9(1-3), 1254-1266.
[http://dx.doi.org/10.2741/1239] [PMID: 14977542]
[29]
Wu, S.S.; Jácamo, R.O.; Vong, S.K.; Rozengurt, E. Differential regulation of Pyk2 phosphorylation at Tyr-402 and Tyr-580 in intestinal epithelial cells: Roles of calcium, Src, Rho kinase, and the cytoskeleton. Cell. Signal., 2006, 18(11), 1932-1940.
[http://dx.doi.org/10.1016/j.cellsig.2006.02.013] [PMID: 16574377]
[30]
Cheng, J.J.; Chao, Y.J.; Wang, D.L. Cyclic strain activates redox-sensitive proline-rich tyrosine kinase 2 (PYK2) in endothelial cells. J. Biol. Chem., 2002, 277(50), 48152-48157.
[http://dx.doi.org/10.1074/jbc.M110937200] [PMID: 12368297]
[31]
Sorokin, A.; Kozlowski, P.; Graves, L.; Philip, A. Protein-tyrosine kinase Pyk2 mediates endothelin-induced p38 MAPK activation in glomerular mesangial cells. J. Biol. Chem., 2001, 276(24), 21521-21528.
[http://dx.doi.org/10.1074/jbc.M008869200] [PMID: 11278444]
[32]
Okigaki, M.; Davis, C.; Falasca, M.; Harroch, S.; Felsenfeld, D.P.; Sheetz, M.P.; Schlessinger, J. Pyk2 regulates multiple signaling events crucial for macrophage morphology and migration. Proc. Natl. Acad. Sci., 2003, 100(19), 10740-10745.
[http://dx.doi.org/10.1073/pnas.1834348100] [PMID: 12960403]
[33]
Sun, C.K.; Ng, K.T.; Lim, Z.X.; Cheng, Q.; Lo, C.M.; Poon, R.T.; Man, K.; Wong, N.; Fan, S.T. Proline-rich tyrosine kinase 2 (Pyk2) promotes cell motility of hepatocellular carcinoma through induction of epithelial to mesenchymal transition. PLoS One, 2011, 6(4), e18878.
[http://dx.doi.org/10.1371/journal.pone.0018878] [PMID: 21533080]
[34]
Gil-Henn, H.; Destaing, O.; Sims, N.A.; Aoki, K.; Alles, N.; Neff, L.; Sanjay, A.; Bruzzaniti, A.; De Camilli, P.; Baron, R.; Schlessinger, J. Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2−/− mice. J. Cell Biol., 2007, 178(6), 1053-1064.
[http://dx.doi.org/10.1083/jcb.200701148] [PMID: 17846174]
[35]
Owen, K.A.; Thomas, K.S.; Bouton, A.H. The differential expression of Yersinia pseudotuberculosis adhesins determines the requirement for FAK and/or Pyk2 during bacterial phagocytosis by macrophages. Cell. Microbiol., 2007, 9(3), 596-609.
[http://dx.doi.org/10.1111/j.1462-5822.2006.00811.x] [PMID: 16987330]
[36]
Koh, Y.H.; Che, W.; Higashiyama, S.; Takahashi, M.; Miyamoto, Y.; Suzuki, K.; Taniguchi, N. Osmotic stress induces HB-EGF gene expression via Ca(2+)/Pyk2/JNK signal cascades in rat aortic smooth muscle cells. J. Biochem., 2001, 130(3), 351-358.
[http://dx.doi.org/10.1093/oxfordjournals.jbchem.a002993] [PMID: 11530010]
[37]
Klemm, A.H.; Kienle, S.; Rheinlaender, J.; Schäffer, T.E.; Goldmann, W.H. The influence of Pyk2 on the mechanical properties in fibroblasts. Biochem. Biophys. Res. Commun., 2010, 393(4), 694-697.
[http://dx.doi.org/10.1016/j.bbrc.2010.02.059] [PMID: 20170630]
[38]
Takahashi, T.; Yamashita, H.; Nagano, Y.; Nakamura, T.; Ohmori, H.; Avraham, H.; Avraham, S.; Yasuda, M.; Matsumoto, M. Identification and characterization of a novel Pyk2/related adhesion focal tyrosine kinase-associated protein that inhibits alpha-synuclein phosphorylation. J. Biol. Chem., 2003, 278(43), 42225-42233.
[http://dx.doi.org/10.1074/jbc.M213217200] [PMID: 12893833]
[39]
Cox, B.D.; Natarajan, M.; Stettner, M.R.; Gladson, C.L. New concepts regarding focal adhesion kinase promotion of cell migration and proliferation. J. Cell. Biochem., 2006, 99(1), 35-52.
[http://dx.doi.org/10.1002/jcb.20956] [PMID: 16823799]
[40]
Hanks, S.K.; Ryzhova, L.; Shin, N.Y.; Brábek, J. Focal adhesion kinase signaling activities and their implications in the control of cell survival and motility. Front. Biosci., 2003, 8(4), 1114.
[http://dx.doi.org/10.2741/1114] [PMID: 12700132]
[41]
Girault, J.A.; Costa, A.; Derkinderen, P.; Studler, J.M.; Toutant, M. FAK and PYK2/CAKβ in the nervous system: A link between neuronal activity, plasticity and survival? Trends Neurosci., 1999, 22(6), 257-263.
[http://dx.doi.org/10.1016/S0166-2236(98)01358-7] [PMID: 10354603]
[42]
Buckbinder, L.; Crawford, D.T.; Qi, H.; Ke, H.Z.; Olson, L.M.; Long, K.R.; Bonnette, P.C.; Baumann, A.P.; Hambor, J.E.; Grasser, W.A., III; Pan, L.C.; Owen, T.A.; Luzzio, M.J.; Hulford, C.A.; Gebhard, D.F.; Paralkar, V.M.; Simmons, H.A.; Kath, J.C.; Roberts, W.G.; Smock, S.L.; Guzman-Perez, A.; Brown, T.A.; Li, M. Proline-rich tyrosine kinase 2 regulates osteoprogenitor cells and bone formation, and offers an anabolic treatment approach for osteoporosis. Proc. Natl. Acad. Sci., 2007, 104(25), 10619-10624.
[http://dx.doi.org/10.1073/pnas.0701421104] [PMID: 17537919]
[43]
Salazar, S.V.; Cox, T.O.; Lee, S.; Brody, A.H.; Chyung, A.S.; Haas, L.T.; Strittmatter, S.M. Alzheimer’s disease risk factor Pyk2 mediates Amyloid-β-induced synaptic dysfunction and loss. J. Neurosci., 2019, 39(4), 758-772.
[http://dx.doi.org/10.1523/JNEUROSCI.1873-18.2018] [PMID: 30518596]
[44]
Lakkakorpi, P.T.; Bett, A.J.; Lipfert, L.; Rodan, G.A.; Duong, L.T. PYK2 autophosphorylation, but not kinase activity, is necessary for adhesion-induced association with c-Src, osteoclast spreading, and bone resorption. J. Biol. Chem., 2003, 278(13), 11502-11512.
[http://dx.doi.org/10.1074/jbc.M206579200] [PMID: 12514172]
[45]
Huang, Y.Q.; Lu, W.Y.; Ali, D.W.; Pelkey, K.A.; Pitcher, G.M.; Lu, Y.M.; Aoto, H.; Roder, J.C.; Sasaki, T.; Salter, M.W.; MacDonald, J.F. CAKbeta/Pyk2 kinase is a signaling link for induction of long-term potentiation in CA1 hippocampus. Neuron, 2001, 29(2), 485-496.
[http://dx.doi.org/10.1016/S0896-6273(01)00220-3] [PMID: 11239437]
[46]
Bartos, J.A.; Ulrich, J.D.; Li, H.; Beazely, M.A.; Chen, Y.; MacDonald, J.F.; Hell, J.W. Postsynaptic clustering and activation of Pyk2 by PSD-95. J. Neurosci., 2010, 30(2), 449-463.
[http://dx.doi.org/10.1523/JNEUROSCI.4992-08.2010] [PMID: 20071509]
[47]
Hsin, H.; Kim, M.J.; Wang, C.F.; Sheng, M. Proline-rich tyrosine kinase 2 regulates hippocampal long-term depression. J. Neurosci., 2010, 30(36), 11983-11993.
[http://dx.doi.org/10.1523/JNEUROSCI.1029-10.2010] [PMID: 20826662]
[48]
Giralt, A.; Brito, V.; Chevy, Q.; Simonnet, C.; Otsu, Y.; Cifuentes-Díaz, C.; de Pins, B.; Coura, R.; Alberch, J.; Ginés, S.; Poncer, J.C.; Girault, J.A. Pyk2 modulates hippocampal excitatory synapses and contributes to cognitive deficits in a Huntington’s disease model. Nat. Commun., 2017, 8(1), 15592.
[http://dx.doi.org/10.1038/ncomms15592] [PMID: 28555636]
[49]
Sharma, D.; Kinsey, W.H. PYK2: A calcium-sensitive protein tyrosine kinase activated in response to fertilization of the zebrafish oocyte. Dev. Biol., 2013, 373(1), 130-140.
[http://dx.doi.org/10.1016/j.ydbio.2012.10.015] [PMID: 23084926]
[50]
Meng, X.Q.; Zheng, K.G.; Yang, Y.; Jiang, M.X.; Zhang, Y.L.; Sun, Q.Y.; Li, Y.L. Proline-rich tyrosine kinase2 is involved in F-actin organization during in vitro maturation of rat oocyte. Reproduction, 2006, 132(6), 859-867.
[http://dx.doi.org/10.1530/rep.1.01212] [PMID: 17127746]
[51]
Battistone, M.A.; Alvau, A.; Salicioni, A.M.; Visconti, P.E.; Da Ros, V.G.; Cuasnicú, P.S. Evidence for the involvement of proline-rich tyrosine kinase 2 in tyrosine phosphorylation downstream of protein kinase A activation during human sperm capacitation. Mol. Hum. Reprod., 2014, 20(11), 1054-1066.
[http://dx.doi.org/10.1093/molehr/gau073] [PMID: 25180269]
[52]
McGinnis, L.K.; Luo, J.; Kinsey, W.H. Protein tyrosine kinase signaling in the mouse oocyte cortex during sperm–egg interactions and anaphase resumption. Mol. Reprod. Dev., 2013, 80(4), 260-272.
[http://dx.doi.org/10.1002/mrd.22160] [PMID: 23401167]
[53]
Luo, J.; McGinnis, L.K.; Carlton, C.; Beggs, H.E.; Kinsey, W.H. PTK2b function during fertilization of the mouse oocyte. Biochem. Biophys. Res. Commun., 2014, 450(3), 1212-1217.
[http://dx.doi.org/10.1016/j.bbrc.2014.03.083] [PMID: 24667605]
[54]
Wang, H.; Luo, J.; Carlton, C.; McGinnis, L.K.; Kinsey, W.H. Sperm-oocyte contact induces outside-in signaling via PYK2 activation. Dev. Biol., 2017, 428(1), 52-62.
[http://dx.doi.org/10.1016/j.ydbio.2017.05.016] [PMID: 28527703]
[55]
Hardy, J.A.; Higgins, G.A. Alzheimer’s disease: The amyloid cascade hypothesis. Science, 1992, 256(5054), 184-185.
[http://dx.doi.org/10.1126/science.1566067] [PMID: 1566067]
[56]
Mosher, K.I.; Wyss-Coray, T. Microglial dysfunction in brain aging and Alzheimer’s disease. Biochem. Pharmacol., 2014, 88(4), 594-604.
[http://dx.doi.org/10.1016/j.bcp.2014.01.008] [PMID: 24445162]
[57]
Hollingworth, P.; Harold, D.; Sims, R.; Gerrish, A.; Lambert, J.C.; Carrasquillo, M.M.; Abraham, R.; Hamshere, M.L.; Pahwa, J.S.; Moskvina, V.; Dowzell, K.; Jones, N.; Stretton, A.; Thomas, C.; Richards, A.; Ivanov, D.; Widdowson, C.; Chapman, J.; Lovestone, S.; Powell, J.; Proitsi, P.; Lupton, M.K.; Brayne, C.; Rubinsztein, D.C.; Gill, M.; Lawlor, B.; Lynch, A.; Brown, K.S.; Passmore, P.A.; Craig, D.; McGuinness, B.; Todd, S.; Holmes, C.; Mann, D.; Smith, A.D.; Beaumont, H.; Warden, D.; Wilcock, G.; Love, S.; Kehoe, P.G.; Hooper, N.M.; Vardy, E.R.L.C.; Hardy, J.; Mead, S.; Fox, N.C.; Rossor, M.; Collinge, J.; Maier, W.; Jessen, F.; Rüther, E.; Schürmann, B.; Heun, R.; Kölsch, H.; van den Bussche, H.; Heuser, I.; Kornhuber, J.; Wiltfang, J.; Dichgans, M.; Frölich, L.; Hampel, H.; Gallacher, J.; Hüll, M.; Rujescu, D.; Giegling, I.; Goate, A.M.; Kauwe, J.S.K.; Cruchaga, C.; Nowotny, P.; Morris, J.C.; Mayo, K.; Sleegers, K.; Bettens, K.; Engelborghs, S.; De Deyn, P.P.; Van Broeckhoven, C.; Livingston, G.; Bass, N.J.; Gurling, H.; McQuillin, A.; Gwilliam, R.; Deloukas, P.; Al-Chalabi, A.; Shaw, C.E.; Tsolaki, M.; Singleton, A.B.; Guerreiro, R.; Mühleisen, T.W.; Nöthen, M.M.; Moebus, S.; Jöckel, K.H.; Klopp, N.; Wichmann, H.E.; Pankratz, V.S.; Sando, S.B.; Aasly, J.O.; Barcikowska, M.; Wszolek, Z.K.; Dickson, D.W.; Graff-Radford, N.R.; Petersen, R.C.; van Duijn, C.M.; Breteler, M.M.B.; Ikram, M.A.; DeStefano, A.L.; Fitzpatrick, A.L.; Lopez, O.; Launer, L.J.; Seshadri, S.; Berr, C.; Campion, D.; Epelbaum, J.; Dartigues, J.F.; Tzourio, C.; Alpérovitch, A.; Lathrop, M.; Feulner, T.M.; Friedrich, P.; Riehle, C.; Krawczak, M.; Schreiber, S.; Mayhaus, M.; Nicolhaus, S.; Wagenpfeil, S.; Steinberg, S.; Stefansson, H.; Stefansson, K.; Snædal, J.; Björnsson, S.; Jonsson, P.V.; Chouraki, V.; Genier-Boley, B.; Hiltunen, M.; Soininen, H.; Combarros, O.; Zelenika, D.; Delepine, M.; Bullido, M.J.; Pasquier, F.; Mateo, I.; Frank-Garcia, A.; Porcellini, E.; Hanon, O.; Coto, E.; Alvarez, V.; Bosco, P.; Siciliano, G.; Mancuso, M.; Panza, F.; Solfrizzi, V.; Nacmias, B.; Sorbi, S.; Bossù, P.; Piccardi, P.; Arosio, B.; Annoni, G.; Seripa, D.; Pilotto, A.; Scarpini, E.; Galimberti, D.; Brice, A.; Hannequin, D.; Licastro, F.; Jones, L.; Holmans, P.A.; Jonsson, T.; Riemenschneider, M.; Morgan, K.; Younkin, S.G.; Owen, M.J.; O’Donovan, M.; Amouyel, P.; Williams, J. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease. Nat. Genet., 2011, 43(5), 429-435.
[http://dx.doi.org/10.1038/ng.803] [PMID: 21460840]
[58]
Beecham, G.W.; Hamilton, K.; Naj, A.C.; Martin, E.R.; Huentelman, M.; Myers, A.J.; Corneveaux, J.J.; Hardy, J.; Vonsattel, J.P.; Younkin, S.G.; Bennett, D.A.; De Jager, P.L.; Larson, E.B.; Crane, P.K.; Kamboh, M.I.; Kofler, J.K.; Mash, D.C.; Duque, L.; Gilbert, J.R.; Gwirtsman, H.; Buxbaum, J.D.; Kramer, P.; Dickson, D.W.; Farrer, L.A.; Frosch, M.P.; Ghetti, B.; Haines, J.L.; Hyman, B.T.; Kukull, W.A.; Mayeux, R.P.; Pericak-Vance, M.A.; Schneider, J.A.; Trojanowski, J.Q.; Reiman, E.M.; Schellenberg, G.D.; Montine, T.J. Genome-wide association meta-analysis of neuropathologic features of Alzheimer’s disease and related dementias. PLoS Genet., 2014, 10(9), e1004606.
[http://dx.doi.org/10.1371/journal.pgen.1004606] [PMID: 25188341]
[59]
Seshadri, S.; Fitzpatrick, A.L.; Ikram, M.A.; DeStefano, A.L.; Gudnason, V.; Boada, M.; Bis, J.C.; Smith, A.V.; Carassquillo, M.M.; Lambert, J.C.; Harold, D.; Schrijvers, E.M.; Ramirez-Lorca, R.; Debette, S.; Longstreth, W.T., Jr; Janssens, A.C.; Pankratz, V.S.; Dartigues, J.F.; Hollingworth, P.; Aspelund, T.; Hernandez, I.; Beiser, A.; Kuller, L.H.; Koudstaal, P.J.; Dickson, D.W.; Tzourio, C.; Abraham, R.; Antunez, C.; Du, Y.; Rotter, J.I.; Aulchenko, Y.S.; Harris, T.B.; Petersen, R.C.; Berr, C.; Owen, M.J.; Lopez-Arrieta, J.; Varadarajan, B.N.; Becker, J.T.; Rivadeneira, F.; Nalls, M.A.; Graff-Radford, N.R.; Campion, D.; Auerbach, S.; Rice, K.; Hofman, A.; Jonsson, P.V.; Schmidt, H.; Lathrop, M.; Mosley, T.H.; Au, R.; Psaty, B.M.; Uitterlinden, A.G.; Farrer, L.A.; Lumley, T.; Ruiz, A.; Williams, J.; Amouyel, P.; Younkin, S.G.; Wolf, P.A.; Launer, L.J.; Lopez, O.L.; van Duijn, C.M.; Breteler, M.M. Genome-wide analysis of genetic loci associated with Alzheimer disease. JAMA, 2010, 303(18), 1832-1840.
[http://dx.doi.org/10.1001/jama.2010.574] [PMID: 20460622]
[60]
Harold, D.; Abraham, R.; Hollingworth, P.; Sims, R.; Gerrish, A.; Hamshere, M.L.; Pahwa, J.S.; Moskvina, V.; Dowzell, K.; Williams, A.; Jones, N.; Thomas, C.; Stretton, A.; Morgan, A.R.; Lovestone, S.; Powell, J.; Proitsi, P.; Lupton, M.K.; Brayne, C.; Rubinsztein, D.C.; Gill, M.; Lawlor, B.; Lynch, A.; Morgan, K.; Brown, K.S.; Passmore, P.A.; Craig, D.; McGuinness, B.; Todd, S.; Holmes, C.; Mann, D.; Smith, A.D.; Love, S.; Kehoe, P.G.; Hardy, J.; Mead, S.; Fox, N.; Rossor, M.; Collinge, J.; Maier, W.; Jessen, F.; Schürmann, B.; Heun, R.; van den Bussche, H.; Heuser, I.; Kornhuber, J.; Wiltfang, J.; Dichgans, M.; Frölich, L.; Hampel, H.; Hüll, M.; Rujescu, D.; Goate, A.M.; Kauwe, J.S.K.; Cruchaga, C.; Nowotny, P.; Morris, J.C.; Mayo, K.; Sleegers, K.; Bettens, K.; Engelborghs, S.; De Deyn, P.P.; Van Broeckhoven, C.; Livingston, G.; Bass, N.J.; Gurling, H.; McQuillin, A.; Gwilliam, R.; Deloukas, P.; Al-Chalabi, A.; Shaw, C.E.; Tsolaki, M.; Singleton, A.B.; Guerreiro, R.; Mühleisen, T.W.; Nöthen, M.M.; Moebus, S.; Jöckel, K.H.; Klopp, N.; Wichmann, H.E.; Carrasquillo, M.M.; Pankratz, V.S.; Younkin, S.G.; Holmans, P.A.; O’Donovan, M.; Owen, M.J.; Williams, J. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat. Genet., 2009, 41(10), 1088-1093.
[http://dx.doi.org/10.1038/ng.440] [PMID: 19734902]
[61]
Bettens, K.; Sleegers, K.; Van Broeckhoven, C. Genetic insights in Alzheimer’s disease. Lancet Neurol., 2013, 12(1), 92-104.
[http://dx.doi.org/10.1016/S1474-4422(12)70259-4] [PMID: 23237904]
[62]
Xiong, W.C.; Macklem, M.; Parsons, J.T. Expression and characterization of splice variants of PYK2, a focal adhesion kinase-related protein. J. Cell Sci., 1998, 111(14), 1981-1991.
[http://dx.doi.org/10.1242/jcs.111.14.1981] [PMID: 9645946]
[63]
Dikic, I.; Dikic, I.; Schlessinger, J. Identification of a new Pyk2 isoform implicated in chemokine and antigen receptor signaling. J. Biol. Chem., 1998, 273(23), 14301-14308.
[http://dx.doi.org/10.1074/jbc.273.23.14301] [PMID: 9603937]
[64]
Lee, S.; Salazar, S.V.; Cox, T.O.; Strittmatter, S.M. Pyk2 signaling through Graf1 and rhoA GTPase is required for amyloid-β oligomer-triggered synapse loss. J. Neurosci., 2019, 39(10), 1910-1929.
[http://dx.doi.org/10.1523/JNEUROSCI.2983-18.2018] [PMID: 30626696]
[65]
Tan, M.S.; Yang, Y.X.; Xu, W.; Wang, H.F.; Tan, L.; Zuo, C.T.; Dong, Q.; Tan, L.; Suckling, J.; Yu, J.T. Associations of Alzheimer’s disease risk variants with gene expression, amyloidosis, tauopathy, and neurodegeneration. Alzheimers Res. Ther., 2021, 13(1), 15.
[http://dx.doi.org/10.1186/s13195-020-00755-7] [PMID: 33419465]
[66]
Kaufman, A.C.; Salazar, S.V.; Haas, L.T.; Yang, J.; Kostylev, M.A.; Jeng, A.T.; Robinson, S.A.; Gunther, E.C.; van Dyck, C.H.; Nygaard, H.B.; Strittmatter, S.M. F yn inhibition rescues established memory and synapse loss in A lzheimer mice. Ann. Neurol., 2015, 77(6), 953-971.
[http://dx.doi.org/10.1002/ana.24394] [PMID: 25707991]
[67]
Dourlen, P.; Fernandez-Gomez, F.J.; Dupont, C.; Grenier-Boley, B.; Bellenguez, C.; Obriot, H.; Caillierez, R.; Sottejeau, Y.; Chapuis, J.; Bretteville, A.; Abdelfettah, F.; Delay, C.; Malmanche, N.; Soininen, H.; Hiltunen, M.; Galas, M-C.; Amouyel, P.; Sergeant, N.; Buée, L.; Lambert, J-C.; Dermaut, B. Functional screening of Alzheimer risk loci identifies PTK2B as an in vivo modulator and early marker of Tau pathology. Mol. Psychiatry, 2017, 22(6), 874-883.
[http://dx.doi.org/10.1038/mp.2016.59] [PMID: 27113998]
[68]
Iulita, M.F.; Bejanin, A.; Vilaplana, E.; Carmona-Iragui, M.; Benejam, B.; Videla, L.; Barroeta, I.; Fernández, S.; Altuna, M.; Pegueroles, J.; Montal, V.; Valldeneu, S.; Giménez, S.; González-Ortiz, S.; Torres, S.; El Bounasri El Bennadi, S.; Padilla, C.; Rozalem Aranha, M.; Estellés, T.; Illán-Gala, I.; Belbin, O.; Valle-Tamayo, N.; Camacho, V.; Blessing, E.; Osorio, R.S.; Videla, S.; Lehmann, S.; Holland, A.J.; Zetterberg, H.; Blennow, K.; Alcolea, D.; Clarimón, J.; Zaman, S.H.; Blesa, R.; Lleó, A.; Fortea, J. Association of biological sex with clinical outcomes and biomarkers of Alzheimer’s disease in adults with Down syndrome. Brain Commun., 2023, 5(2), fcad074.
[http://dx.doi.org/10.1093/braincomms/fcad074] [PMID: 37056479]
[69]
Weaver, D.F. Alzheimer’s disease as an innate autoimmune disease (AD2 ): A new molecular paradigm. Alzheimers Dement., 2023, 19(3), 1086-1098.
[http://dx.doi.org/10.1002/alz.12789] [PMID: 36165334]
[70]
Mackenzie, I.R.A.; Munoz, D.G. Nonsteroidal anti-inflammatory drug use and Alzheimer-type pathology in aging. Neurology, 1998, 50(4), 986-990.
[http://dx.doi.org/10.1212/WNL.50.4.986] [PMID: 9566383]
[71]
Combs, C.K.; Johnson, D.E.; Cannady, S.B.; Lehman, T.M.; Landreth, G.E. Identification of microglial signal transduction pathways mediating a neurotoxic response to amyloidogenic fragments of beta-amyloid and prion proteins. J. Neurosci., 1999, 19(3), 928-939.
[http://dx.doi.org/10.1523/JNEUROSCI.19-03-00928.1999] [PMID: 9920656]
[72]
Forloni, G.; Angeretti, N.; Chiesa, R.; Monzani, E.; Salmona, M.; Bugiani, O.; Tagliavini, F. Neurotoxicity of a prion protein fragment. Nature, 1993, 362(6420), 543-546.
[http://dx.doi.org/10.1038/362543a0] [PMID: 8464494]
[73]
Giulian, D.; Haverkamp, L.J.; Li, J.; Karshin, W.L.; Yu, J.; Tom, D.; Li, X.; Kirkpatrick, J.B. Senile plaques stimulate microglia to release a neurotoxin found in Alzheimer brain. Neurochem. Int., 1995, 27(1), 119-137.
[http://dx.doi.org/10.1016/0197-0186(95)00067-I] [PMID: 7655344]
[74]
Brown, D.R.; Schmidt, B.; Kretzschmar, H.A. Role of microglia and host prion protein in neurotoxicity of a prion protein fragment. Nature, 1996, 380(6572), 345-347.
[http://dx.doi.org/10.1038/380345a0] [PMID: 8598929]
[75]
Klegeris, A.; McGeer, P.L. β-Amyloid protein enhances macrophage production of oxygen free radicals and glutamate. J. Neurosci. Res., 1997, 49(2), 229-235.
[http://dx.doi.org/10.1002/(SICI)1097-4547(19970715)49:2<229::AID-JNR11>3.0.CO;2-W] [PMID: 9272645]
[76]
McDonald, D.R.; Brunden, K.R.; Landreth, G.E. Amyloid fibrils activate tyrosine kinase-dependent signaling and superoxide production in microglia. J. Neurosci., 1997, 17(7), 2284-2294.
[http://dx.doi.org/10.1523/JNEUROSCI.17-07-02284.1997] [PMID: 9065490]
[77]
Chung, I.C.; OuYang, C.N.; Yuan, S.N.; Li, H.P.; Chen, J.T.; Shieh, H.R.; Chen, Y.J.; Ojcius, D.M.; Chu, C.L.; Yu, J.S.; Chang, Y.S.; Chen, L.C. Pyk2 activates the NLRP3 inflammasome by directly phosphorylating ASC and contributes to inflammasome-dependent peritonitis. Sci. Rep., 2016, 6(1), 36214.
[http://dx.doi.org/10.1038/srep36214] [PMID: 27796369]
[78]
Halle, A.; Hornung, V.; Petzold, G.C.; Stewart, C.R.; Monks, B.G.; Reinheckel, T.; Fitzgerald, K.A.; Latz, E.; Moore, K.J.; Golenbock, D.T. The NALP3 inflammasome is involved in the innate immune response to amyloid-β. Nat. Immunol., 2008, 9(8), 857-865.
[http://dx.doi.org/10.1038/ni.1636] [PMID: 18604209]
[79]
Tan, M.S.; Yu, J.T.; Jiang, T.; Zhu, X.C.; Tan, L. The NLRP3 inflammasome in Alzheimer’s disease. Mol. Neurobiol., 2013, 48(3), 875-882.
[http://dx.doi.org/10.1007/s12035-013-8475-x] [PMID: 23686772]
[80]
Yoshiyama, Y.; Higuchi, M.; Zhang, B.; Huang, S.M.; Iwata, N.; Saido, T.C.; Maeda, J.; Suhara, T.; Trojanowski, J.Q.; Lee, V.M.Y. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron, 2007, 53(3), 337-351.
[http://dx.doi.org/10.1016/j.neuron.2007.01.010] [PMID: 17270732]
[81]
Bellucci, A.; Westwood, A.J.; Ingram, E.; Casamenti, F.; Goedert, M.; Spillantini, M.G. Induction of inflammatory mediators and microglial activation in mice transgenic for mutant human P301S tau protein. Am. J. Pathol., 2004, 165(5), 1643-1652.
[http://dx.doi.org/10.1016/S0002-9440(10)63421-9] [PMID: 15509534]
[82]
Ikeda, M.; Shoji, M.; Kawarai, T.; Kawarabayashi, T.; Matsubara, E.; Murakami, T.; Sasaki, A.; Tomidokoro, Y.; Ikarashi, Y.; Kuribara, H.; Ishiguro, K.; Hasegawa, M.; Yen, S.H.; Chishti, M.A.; Harigaya, Y.; Abe, K.; Okamoto, K.; St George-Hyslop, P.; Westaway, D. Accumulation of filamentous tau in the cerebral cortex of human tau R406W transgenic mice. Am. J. Pathol., 2005, 166(2), 521-531.
[http://dx.doi.org/10.1016/S0002-9440(10)62274-2] [PMID: 15681835]
[83]
Li, Y.; Liu, L.; Barger, S.W.; Griffin, W.S.T. Interleukin-1 mediates pathological effects of microglia on tau phosphorylation and on synaptophysin synthesis in cortical neurons through a p38-MAPK pathway. J. Neurosci., 2003, 23(5), 1605-1611.
[http://dx.doi.org/10.1523/JNEUROSCI.23-05-01605.2003] [PMID: 12629164]
[84]
Kitazawa, M.; Oddo, S.; Yamasaki, T.R.; Green, K.N.; LaFerla, F.M. Lipopolysaccharide-induced inflammation exacerbates tau pathology by a cyclin-dependent kinase 5-mediated pathway in a transgenic model of Alzheimer’s disease. J. Neurosci., 2005, 25(39), 8843-8853.
[http://dx.doi.org/10.1523/JNEUROSCI.2868-05.2005] [PMID: 16192374]
[85]
Takeuchi, H.; Mizuno, T.; Zhang, G.; Wang, J.; Kawanokuchi, J.; Kuno, R.; Suzumura, A. Neuritic beading induced by activated microglia is an early feature of neuronal dysfunction toward neuronal death by inhibition of mitochondrial respiration and axonal transport. J. Biol. Chem., 2005, 280(11), 10444-10454.
[http://dx.doi.org/10.1074/jbc.M413863200] [PMID: 15640150]
[86]
Pascoal, T.A.; Benedet, A.L.; Ashton, N.J.; Kang, M.S.; Therriault, J.; Chamoun, M.; Savard, M.; Lussier, F.Z.; Tissot, C.; Karikari, T.K.; Ottoy, J.; Mathotaarachchi, S.; Stevenson, J.; Massarweh, G.; Schöll, M.; de Leon, M.J.; Soucy, J.P.; Edison, P.; Blennow, K.; Zetterberg, H.; Gauthier, S.; Rosa-Neto, P. Microglial activation and tau propagate jointly across Braak stages. Nat. Med., 2021, 27(9), 1592-1599.
[http://dx.doi.org/10.1038/s41591-021-01456-w] [PMID: 34446931]
[87]
Tan, M.S.; Liu, Y.; Hu, H.; Tan, C.C.; Tan, L. Inhibition of caspase-1 ameliorates tauopathy and rescues cognitive impairment in SAMP8 mice. Metab. Brain Dis., 2022, 37(4), 1197-1205.
[http://dx.doi.org/10.1007/s11011-022-00914-9] [PMID: 35143023]
[88]
Ghosh, S.; Wu, M.D.; Shaftel, S.S.; Kyrkanides, S.; LaFerla, F.M.; Olschowka, J.A.; O’Banion, M.K. Sustained interleukin-1β overexpression exacerbates tau pathology despite reduced amyloid burden in an Alzheimer’s mouse model. J. Neurosci., 2013, 33(11), 5053-5064.
[http://dx.doi.org/10.1523/JNEUROSCI.4361-12.2013] [PMID: 23486975]
[89]
Rich, J.B.; Rasmusson, D.X.; Folstein, M.F.; Carson, K.A.; Kawas, C.; Brandt, J. Nonsteroidal anti-inflammatory drugs in Alzheimer’s disease. Neurology, 1995, 45(1), 51-55.
[http://dx.doi.org/10.1212/WNL.45.1.51] [PMID: 7824134]
[90]
McGEER, P.L.; McGEER, E.G. Anti-inflammatory drugs in the fight against Alzheimer’s disease. Ann. N. Y. Acad. Sci., 1996, 777(1), 213-220.
[http://dx.doi.org/10.1111/j.1749-6632.1996.tb34421.x] [PMID: 8624086]
[91]
McGeer, P.L.; Schulzer, M.; McGeer, E.G. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease. Neurology, 1996, 47(2), 425-432.
[http://dx.doi.org/10.1212/WNL.47.2.425] [PMID: 8757015]
[92]
Stewart, W.F.; Kawas, C.; Corrada, M.; Metter, E.J. Risk of Alzheimer’s disease and duration of NSAID use. Neurology, 1997, 48(3), 626-632.
[http://dx.doi.org/10.1212/WNL.48.3.626] [PMID: 9065537]

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