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Current Neuropharmacology

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ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

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Systematic Review Article

Lipids as Early and Minimally Invasive Biomarkers for Alzheimer’s Disease

Author(s): Esther Casas-Fernández, Carmen Peña-Bautista, Miguel Baquero and Consuelo Cháfer-Pericás*

Volume 20, Issue 8, 2022

Published on: 11 April, 2022

Page: [1613 - 1631] Pages: 19

DOI: 10.2174/1570159X19666211102150955

Price: $65

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disorder worldwide. Specifically, typical late-onset AD is a sporadic form with a complex etiology that affects over 90% of patients. The current gold standard for AD diagnosis is based on the determination of amyloid status by analyzing cerebrospinal fluid samples or brain positron emission tomography. These procedures can be used widely as they have several disadvantages (expensive, invasive). As an alternative, blood metabolites have recently emerged as promising AD biomarkers. Small molecules that cross the compromised AD blood-brain barrier could be determined in plasma to improve clinical AD diagnosis at early stages through minimally invasive techniques. Specifically, lipids could play an important role in AD since the brain has a high lipid content, and they are present ubiquitously inside amyloid plaques. Therefore, a systematic review was performed with the aim of identifying blood lipid metabolites as potential early AD biomarkers. In conclusion, some lipid families (fatty acids, glycerolipids, glycerophospholipids, sphingolipids, lipid peroxidation compounds) have shown impaired levels at early AD stages. Ceramide levels were significantly higher in AD subjects, and polyunsaturated fatty acids levels were significantly lower in AD. Also, high arachidonic acid levels were found in AD patients in contrast to low sphingomyelin levels. Consequently, these lipid biomarkers could be used for minimally invasive and early AD clinical diagnosis.

Keywords: Alzheimer’s disease, blood, lipid, biomarker, diagnosis, PET.

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[1]
Martin, P.A.; Wimo, A.; Guerchet, M.; Gemma-Claire Ali, M.; Wu, Y-T.; Prina, M. World Alzheimer Report 2015. The global impact of dementia an analysIs of prevalence, incidence, cost and trends Alzheimer’s Disease International; ADI: London, UK, 2015.
[2]
El, F.; Jing, P.; Xia, J.; Cai, D. Alzheimer ’ s disease risk genes and lipid regulators. Alzheimers Dis, 2016, 53, 15-29.
[http://dx.doi.org/10.3233/JAD-160169]
[3]
Wang, G.; Bieberich, E. Sphingolipids in neurodegeneration (with focus on ceramide and S1P). Adv. Biol. Regul., 2018, 70, 51-64.
[http://dx.doi.org/10.1016/j.jbior.2018.09.013] [PMID: 30287225]
[4]
Penke, B. Bogár, F.; Fülöp, L. β-Amyloid and the Pathomechanisms of Alzheimer’s Disease: A Comprehensive View. Molecules, 2017, 22(10), 1692.
[http://dx.doi.org/10.3390/molecules22101692] [PMID: 28994715]
[5]
Kao, Y.C.; Ho, P.C.; Tu, Y.K.; Jou, I.M.; Tsai, K.J. Lipids and Alzheimer’s disease. Int. J. Mol. Sci., 2020, 21.
[6]
Jack, C.R.; Bennett, D.A.; Blennow, K.; Carrillo, M.C.; Dunn, B.; Haeberlein, S.B. NIA-AA research framework: Toward a biological defi-nition of Alzheimer’s disease. Alzheimer’s and Dementia, 2018, 14, 535-562.
[7]
Mapstone, M.; Cheema, A.K.; Fiandaca, M.S.; Zhong, X.; Mhyre, T.R.; MacArthur, L.H.; Hall, W.J.; Fisher, S.G.; Peterson, D.R.; Haley, J.M.; Nazar, M.D.; Rich, S.A.; Berlau, D.J.; Peltz, C.B.; Tan, M.T.; Kawas, C.H.; Federoff, H.J. Plasma phospholipids identify antecedent memory impairment in older adults. Nat. Med., 2014, 20(4), 415-418.
[http://dx.doi.org/10.1038/nm.3466] [PMID: 24608097]
[8]
Grasso, G. Mass spectrometry is a multifaceted weapon to be used in the battle against Alzheimer’s disease: Amyloid beta peptides and beyond. Mass Spectrom. Rev., 2019, 38(1), 34-48.
[http://dx.doi.org/10.1002/mas.21566] [PMID: 29905953]
[9]
Bachhuber, F.; Tumani, H. The cerebrospinal fluid and barriers – anatomic and physiologic considerations. Handb. Clin. Neurol., 2018, 146.
[10]
Zlokovic, B.V. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat. Rev. Neurosci., 2011, 12(12), 723-738.
[http://dx.doi.org/10.1038/nrn3114] [PMID: 22048062]
[11]
Hussain, G.; Anwar, H.; Rasul, A.; Imran, A.; Qasim, M.; Zafar, S. Lipids as biomarkers of brain disorders. Crit. Rev. Food Sci. Nutr., 2019, 83-98.
[PMID: 30614244]
[12]
Michalicova, A.; Majerova, P.; Kovac, A.; Alonso, A. Tau protein and its role in blood – brain barrier dysfunction. Front. Mol. Neurosci., 2020, 13(September), 570045.
[http://dx.doi.org/10.3389/fnmol.2020.570045] [PMID: 33100967]
[13]
Wang, Y.C.; Lauwers, E.; Verstreken, P. Presynaptic protein homeostasis and neuronal function. Curr. Opin. Genet. Dev., 2017, 44, 38-46.
[14]
Rosenberg, G.A. Blood-brain barrier permeability in aging and Alzheimer’s disease. J. Prev. Alzheimers Dis., 2014, 1(3), 138-139.
[PMID: 26301207]
[15]
Jannic, B.; Karl, F.; Nicole, L.; Richard, R. The neurobiology of aging and Alzheimer’s disease: walking down the same road? Eur. J. Neurosci., 2013, 37(12), 1885-1886.
[http://dx.doi.org/10.1111/ejn.12261] [PMID: 23773056]
[16]
Montagne, A.; Barnes, S.R.; Sweeney, M.D.; Halliday, M.R.; Sagare, A.P.; Zhao, Z.; Toga, A.W.; Jacobs, R.E.; Liu, C.Y.; Amezcua, L.; Harrington, M.G.; Chui, H.C.; Law, M.; Zlokovic, B.V. Blood-brain barrier breakdown in the aging human hippocampus. Neuron, 2015, 85(2), 296-302.
[http://dx.doi.org/10.1016/j.neuron.2014.12.032] [PMID: 25611508]
[17]
Sweeney, M.D.; Sagare, A.P.; Zlokovic, B.V. Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat. Rev. Neurol., 2018, 14, 133-150.
[18]
de la Torre, J.C. Vascular risk factor detection and control may prevent Alzheimer’s disease. Ageing Res. Rev., 2010, 9(3), 218-225.
[http://dx.doi.org/10.1016/j.arr.2010.04.002] [PMID: 20385255]
[19]
Hampel, H.; O’Bryant, S.E.; Molinuevo, J.L.; Zetterberg, H.; Masters, C.L.; Lista, S. Blood-based biomarkers for Alzheimer disease: map-ping the road to the clinic. Nat. Rev. Neurol., 2018, 14, 639-652.
[20]
Ding, X.; Zhang, S.; Jiang, L.; Wang, L.; Li, T.; Lei, P. Ultrasensitive assays for detection of plasma tau and phosphorylated tau 181 in Alzheimer’s disease: a systematic review and meta-analysis. Transl. Neurodegener., 2021, 10(1), 10.
[http://dx.doi.org/10.1186/s40035-021-00234-5] [PMID: 33712071]
[21]
Thijssen, E.H.; Verberk, I.M.W.; Vanbrabant, J.; Koelewijn, A.; Heijst, H.; Scheltens, P.; van der Flier, W.; Vanderstichele, H.; Stoops, E.; Teunissen, C.E. Highly specific and ultrasensitive plasma test detects Abeta(1-42) and Abeta(1-40) in Alzheimer’s disease. Sci. Rep., 2021, 11(1), 9736.
[http://dx.doi.org/10.1038/s41598-021-89004-x] [PMID: 33958661]
[22]
Blennow, K.; Zetterberg, H. Biomarkers for Alzheimer’s disease: current status and prospects for the future. J. Intern. Med., 2018, 284, 643-663.
[23]
Naudí, A.; Cabré, R.; Jové, M.; Ayala, V.; Gonzalo, H.; Portero-Otín, M. Lipidomics of Human Brain Aging and Alzheimer’s Disease Pa-thology. Int. Rev. Neurobiol., 2015, 133-189.
[24]
Peña-bautista, C.; Vigor, C.; Galano, J.; Oger, C.; Durand, T.; Ferrer, I. Free radical biology and medicine plasma lipid peroxidation bi-omarkers for early and non-invasive Alzheimer’s disease detection. Free Radic. Biol. Med., 2018, 124, 388-394.
[http://dx.doi.org/10.1016/j.freeradbiomed.2018.06.038] [PMID: 29969716]
[25]
Peña-Bautista, C.; Roca, M.; Hervás, D.; Cuevas, A.; López-Cuevas, R.; Vento, M.; Baquero, M.; García-Blanco, A.; Cháfer-Pericás, C. Plasma metabolomics in early Alzheimer’s disease patients diagnosed with amyloid biomarker. J. Proteomics, 2019, 200(January), 144-152.
[http://dx.doi.org/10.1016/j.jprot.2019.04.008] [PMID: 30978462]
[26]
Padurariu, M.; Ciobica, A.; Hritcu, L.; Stoica, B.; Bild, W.; Stefanescu, C. Changes of some oxidative stress markers in the serum of pa-tients with mild cognitive impairment and Alzheimer’s disease. Neurosci. Lett., 2010, 469(1), 6-10.
[http://dx.doi.org/10.1016/j.neulet.2009.11.033] [PMID: 19914330]
[27]
Ademowo, O.S.; Dias, H.K.I.; Milic, I.; Devitt, A.; Moran, R.; Mulcahy, R. Phospholipid oxidation and carotenoid supplementation in Alz-heimer’s disease patients. Free Radic. Biol. Med., 2017, 108, 77-85.
[http://dx.doi.org/10.1016/j.freeradbiomed.2017.03.008]
[28]
Morgado, I.; Garvey, M. Lipids in Amyloid-β processing, aggregation, and toxicity. Adv. Exp. Med. Biol., 2015, 855, 67-94.
[http://dx.doi.org/10.1007/978-3-319-17344-3_3] [PMID: 26149926]
[29]
Mattson, M.P.; Cutler, R.G.; Jo, D.G. Alzheimer peptides perturb lipid-regulating enzymes. Nat. Cell Biol., 2005, 7(11), 1045-1047.
[http://dx.doi.org/10.1038/ncb1105-1045] [PMID: 16385731]
[30]
Martín, V.; Fabelo, N.; Santpere, G.; Puig, B.; Marín, R.; Ferrer, I.; Díaz, M. Lipid alterations in lipid rafts from Alzheimer’s disease hu-man brain cortex. J. Alzheimers Dis., 2010, 19(2), 489-502.
[http://dx.doi.org/10.3233/JAD-2010-1242] [PMID: 20110596]
[31]
Rebeck, G.W. The role of APOE on lipid homeostasis and inflammation in normal brains. J. Lipid Res., 2017, 58(8), 1493-1499.
[http://dx.doi.org/10.1194/jlr.R075408] [PMID: 28258087]
[32]
Bernath, M.M.; Bhattacharyya, S.; Nho, K.; Barupal, D.K.; Fiehn, O.; Baillie, R.; Risacher, S.L.; Arnold, M.; Jacobson, T.; Trojanowski, J.Q.; Shaw, L.M.; Weiner, M.W.; Doraiswamy, P.M.; Kaddurah-Daouk, R.; Saykin, A.J. Serum triglycerides in Alzheimer disease: Relation to neuroimaging and CSF biomarkers. Neurology, 2020, 94(20), e2088-e2098.
[http://dx.doi.org/10.1212/WNL.0000000000009436] [PMID: 32358220]
[33]
Barupal, D.K.; Baillie, R.; Fan, S.; Saykin, A.J.; Meikle, P.J.; Arnold, M. Sets of coregulated serum lipids are associated with Alzheimer’s disease pathophysiology. Alzheimer’s Dement. Diagnosis, Assess. Dis. Mon., 2019, 11, 619-627.
[http://dx.doi.org/10.1016/j.dadm.2019.07.002]
[34]
Fahy, E.; Subramaniam, S.; Brown, H.A.; Glass, C.K.; Merrill, A.H., Jr; Murphy, R.C.; Raetz, C.R.; Russell, D.W.; Seyama, Y.; Shaw, W.; Shimizu, T.; Spener, F.; van Meer, G.; VanNieuwenhze, M.S.; White, S.H.; Witztum, J.L.; Dennis, E.A. A comprehensive classification system for lipids. J. Lipid Res., 2005, 46(5), 839-861.
[http://dx.doi.org/10.1194/jlr.E400004-JLR200] [PMID: 15722563]
[35]
Fahy, E.; Subramaniam, S.; Murphy, R.C.; Nishijima, M.; Raetz, C.R.H.; Shimizu, T. Update of the LIPID MAPS comprehensive classification system for lipids. J. Lipid Res., 2009, 50, 59.
[36]
Touboul, D.; Gaudin, M. Lipidomics of Alzheimer’s disease. Bioanalysis, 2014, 6(4), 541-561.
[http://dx.doi.org/10.4155/bio.13.346] [PMID: 24568356]
[37]
Craig-Schapiro, R.; Fagan, A.M.; Holtzman, D.M. Biomarkers of Alzheimer’s disease. Neurobiol. Dis., 2009, 35(2), 128-140.
[PMID: 19010417]
[38]
Proitsi, P.; Kim, M.; Whiley, L.; Simmons, A.; Sattlecker, M.; Velayudhan, L.; Lupton, M.K.; Soininen, H.; Kloszewska, I.; Mecocci, P.; Tsolaki, M.; Vellas, B.; Lovestone, S.; Powell, J.F.; Dobson, R.J.; Legido-Quigley, C. Association of blood lipids with Alzheimer’s dis-ease: A comprehensive lipidomics analysis. Alzheimers Dement., 2017, 13(2), 140-151.
[http://dx.doi.org/10.1016/j.jalz.2016.08.003] [PMID: 27693183]
[39]
Barrier, B.B.; Van Dyken, P.; Lacoste, B.; Talbot, S.; Menard, C. Impact of metabolic syndrome on neuroinflammation. Front. Neurosci., 2018, 12, 1-19.
[40]
Bazinet, R.P.; Layé, S. Polyunsaturated fatty acids and their metabolites in brain function and disease. Nat. Rev. Neurosci., 2014, 15, 771-785.
[41]
Salem, N.; Vandal, M.; Calon, F. The benefit of docosahexaenoic acid for the adult brain in aging and dementia. Prostaglandins Leukot. Essent. Fatty Acids, 2015, 92, 15-22.
[http://dx.doi.org/10.1016/j.plefa.2014.10.003]
[42]
Patrick, R.P. Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer’s disease. FASEB J., 2019, 33(2), 1554-1564.
[http://dx.doi.org/10.1096/fj.201801412R] [PMID: 30289748]
[43]
Wang, D.C.; Sun, C.H.; Liu, L.Y.; Sun, X.H.; Jin, X.W.; Song, W.L.; Liu, X.Q.; Wan, X.L. Serum fatty acid profiles using GC-MS and multivariate statistical analysis: potential biomarkers of Alzheimer’s disease. Neurobiol. Aging, 2012, 33(6), 1057-1066.
[http://dx.doi.org/10.1016/j.neurobiolaging.2010.09.013] [PMID: 20980076]
[44]
Olazarán, J.; Gil-de-Gómez, L.; Rodríguez-Martín, A.; Valentí-Soler, M.; Frades-Payo, B.; Marín-Muñoz, J.; Antúnez, C.; Frank-García, A.; Acedo-Jiménez, C.; Morlán-Gracia, L.; Petidier-Torregrossa, R.; Guisasola, M.C.; Bermejo-Pareja, F.; Sánchez-Ferro, Á.; Pérez-Martínez, D.A.; Manzano-Palomo, S.; Farquhar, R.; Rábano, A.; Calero, M. A blood-based, 7-metabolite signature for the early diagnosis of Alz-heimer’s disease. J. Alzheimers Dis., 2015, 45(4), 1157-1173.
[http://dx.doi.org/10.3233/JAD-142925] [PMID: 25649659]
[45]
Goozee, K.; Chatterjee, P.; James, I.; Shen, K.; Sohrabi, H.R.; Asih, P.R.; Dave, P.; Ball, B.; ManYan, C.; Taddei, K.; Chung, R.; Garg, M.L.; Martins, R.N. Alterations in erythrocyte fatty acid composition in preclinical Alzheimer’s disease. Sci. Rep., 2017, 7(1), 676.
[http://dx.doi.org/10.1038/s41598-017-00751-2] [PMID: 28386119]
[46]
Abdullah, L.; Evans, J.E.; Emmerich, T.; Crynen, G.; Shackleton, B.; Keegan, A.P. APOE ε4 specific imbalance of arachidonic acid and docosahexaenoic acid in serum phospholipids identifies individuals with preclinical mild cognitive impairment/Alzheimer’s disease. Aging (Albany NY), 2017, 9(3), 964-985.
[47]
Whiley, L.; Sen, A.; Heaton, J.; Proitsi, P.; García-Gómez, D.; Leung, R.; Smith, N.; Thambisetty, M.; Kloszewska, I.; Mecocci, P.; Soin-inen, H.; Tsolaki, M.; Vellas, B.; Lovestone, S.; Legido-Quigley, C. Evidence of altered phosphatidylcholine metabolism in Alzheimer’s disease. Neurobiol. Aging, 2014, 35(2), 271-278.
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.08.001] [PMID: 24041970]
[48]
Wang, G.; Zhou, Y.; Huang, F.J.; Tang, H.D.; Xu, X.H.; Liu, J.J.; Wang, Y.; Deng, Y.L.; Ren, R.J.; Xu, W.; Ma, J.F.; Zhang, Y.N.; Zhao, A.H.; Chen, S.D.; Jia, W. Plasma metabolite profiles of Alzheimer’s disease and mild cognitive impairment. J. Proteome Res., 2014, 13(5), 2649-2658.
[http://dx.doi.org/10.1021/pr5000895] [PMID: 24694177]
[49]
Xicota, L.; Ichou, F.; Lejeune, F.X.; Colsch, B.; Tenenhaus, A.; Leroy, I.; Fontaine, G.; Lhomme, M.; Bertin, H.; Habert, M.O.; Epelbaum, S.; Dubois, B.; Mochel, F.; Potier, M.C. Multi-omics signature of brain amyloid deposition in asymptomatic individuals at-risk for Alz-heimer’s disease: The INSIGHT-preAD study. EBioMedicine, 2019, 47, 518-528.
[http://dx.doi.org/10.1016/j.ebiom.2019.08.051] [PMID: 31492558]
[50]
Lin, C.N.; Huang, C.C.; Huang, K.L.; Lin, K.J.; Yen, T.C.; Kuo, H.C. A metabolomic approach to identifying biomarkers in blood of Alz-heimer’s disease. Ann. Clin. Transl. Neurol., 2019, 6(3), 537-545.
[http://dx.doi.org/10.1002/acn3.726]
[51]
Al-khateeb, E.; Althaher, A.; Al-khateeb, M.; Al-Musawi, H.; Azzouqah, O.; Al-Shweiki, S.; Shafagoj, Y. Relation between uric acid and Alzheimer’s disease in elderly Jordanians. J. Alzheimers Dis., 2015, 44(3), 859-865.
[http://dx.doi.org/10.3233/JAD-142037] [PMID: 25362039]
[52]
de Leeuw, F.A.; Peeters, C.F.W.; Kester, M.I.; Harms, A.C.; Struys, E.A.; Hankemeier, T.; van Vlijmen, H.W.T.; van der Lee, S.J.; van Duijn, C.M.; Scheltens, P.; Demirkan, A.; van de Wiel, M.A.; van der Flier, W.M.; Teunissen, C.E. Blood-based metabolic signatures in Alzheimer’s disease. Alzheimers Dement. (Amst.), 2017, 8, 196-207.
[http://dx.doi.org/10.1016/j.dadm.2017.07.006] [PMID: 28951883]
[53]
Kim, S.H.; Yang, J.S.; Lee, J.C.; Lee, J.Y.; Lee, J.Y.; Kim, E.; Moon, M.H. Lipidomic alterations in lipoproteins of patients with mild cog-nitive impairment and Alzheimer’s disease by asymmetrical flow field-flow fractionation and nanoflow ultrahigh performance liquid chromatography-tandem mass spectrometry. J. Chromatogr. A, 2018, 1568, 91-100.
[http://dx.doi.org/10.1016/j.chroma.2018.07.018] [PMID: 30007793]
[54]
Anand, S.; Barnes, J.M.; Young, S.A.; Garcia, D.M.; Tolley, H.D.; Kauwe, J.S.K.; Graves, S.W. Discovery and confirmation of diagnostic serum lipid biomarkers for Alzheimer’s disease using direct infusion mass spectrometry. J. Alzheimers Dis., 2017, 59(1), 277-290.
[PMID: 28598845]
[55]
Kim, M.; Nevado-Holgado, A.; Whiley, L.; Snowden, S.G.; Soininen, H.; Kloszewska, I.; Mecocci, P.; Tsolaki, M.; Vellas, B.; Thambi-setty, M.; Dobson, R.J.B.; Powell, J.F.; Lupton, M.K.; Simmons, A.; Velayudhan, L.; Lovestone, S.; Proitsi, P.; Legido-Quigley, C. Associ-ation between plasma ceramides and phosphatidylcholines and hippocampal brain volume in late onset Alzheimer’s disease. J. Alzheimers Dis., 2017, 60(3), 809-817.
[http://dx.doi.org/10.3233/JAD-160645] [PMID: 27911300]
[56]
Varma, V.R.; Oommen, A.M.; Varma, S.; Casanova, R.; An, Y.; Andrews, R.M. Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: A targeted metabolomics study. PLoS Med., 2018, 15(1), e1002482.
[57]
Costa, A.C.; Joaquim, H.P.G.; Forlenza, O.; Talib, L.L.; Gattaz, W.F. Plasma lipids metabolism in mild cognitive impairment and Alz-heimer’s disease. World J. Biol. Psychiatry, 2019, 20(3), 190-196.
[http://dx.doi.org/10.1080/15622975.2017.1369566] [PMID: 28922966]
[58]
Oberacher, H.; Arnhard, K.; Linhart, C.; Diwo, A.; Marksteiner, J.; Humpel, C. Targeted metabolomic analysis of soluble lysates from platelets of patients with mild cognitive impairment and Alzheimer’s Disease compared to healthy controls: Is PC aeC40:4 a promising di-agnostic tool? J. Alzheimers Dis., 2017, 57(2), 493-504.
[http://dx.doi.org/10.3233/JAD-160172] [PMID: 28269764]
[59]
Arnold, M.; Nho, K.; Kueider-Paisley, A.; Massaro, T.; Huynh, K.; Brauner, B. Sex and APOE ε4 genotype modify the Alzheimer’s dis-ease serum metabolome. Nat. Commun., 2020, 11(1), 148.
[http://dx.doi.org/10.1038/s41467-020-14959-w]
[60]
Peña-Bautista, C.; Roca, M.; López-Cuevas, R.; Baquero, M.; Vento, M.; Cháfer-Pericás, C. Metabolomics study to identify plasma bi-omarkers in Alzheimer disease: ApoE genotype effect. J. Pharm. Biomed. Anal., 2020, 180, 113088.
[http://dx.doi.org/10.1016/j.jpba.2019.113088] [PMID: 31923717]
[61]
González-Domínguez, R.; García-Barrera, T.; Gómez-Ariza, J.L. Combination of metabolomic and phospholipid-profiling approaches for the study of Alzheimer’s disease. J. Proteomics, 2014, 104, 37-47.
[http://dx.doi.org/10.1016/j.jprot.2014.01.014] [PMID: 24473279]
[62]
García-Ruiz, C.; Colell, A.; Marí, M.; Morales, A.; Fernández-Checa, J.C. Direct effect of ceramide on the mitochondrial electron transport chain leads to generation of reactive oxygen species. Role of mitochondrial glutathione. J. Biol. Chem., 1997, 272(17), 11369-11377.
[http://dx.doi.org/10.1074/jbc.272.17.11369] [PMID: 9111045]
[63]
Hernandez-Diaz, S.; Soukup, S.F. The role of lipids in autophagy and its implication in neurodegeneration. Cell Stress, 2020, 4(7), 167-186.
[http://dx.doi.org/10.15698/cst2020.07.225] [PMID: 32656499]
[64]
Mielke, M.M.; Haughey, N.J.; Han, D.; An, Y.; Bandaru, V.V.R.; Lyketsos, C.G.; Ferrucci, L.; Resnick, S.M. The association between plasma ceramides and sphingomyelins and risk of Alzheimer’s disease differs by sex and APOE in the baltimore longitudinal study of ag-ing. J. Alzheimers Dis., 2017, 60(3), 819-828.
[http://dx.doi.org/10.3233/JAD-160925] [PMID: 28035934]
[65]
Mielke, M.M.; Haughey, N.J.; Bandaru, V.V.; Schech, S.; Carrick, R.; Carlson, M.C.; Mori, S.; Miller, M.I.; Ceritoglu, C.; Brown, T.; Al-bert, M.; Lyketsos, C.G. Plasma ceramides are altered in mild cognitive impairment and predict cognitive decline and hippocampal volume loss. Alzheimers Dement., 2010, 6(5), 378-385.
[http://dx.doi.org/10.1016/j.jalz.2010.03.014] [PMID: 20813340]
[66]
Alessenko, A.V.; Albi, E. Exploring Sphingolipid Implications in Neurodegeneration. Front. Neurol., 2020, 11, 437.
[http://dx.doi.org/10.3389/fneur.2020.00437] [PMID: 32528400]
[67]
Han, X.; Rozen, S.; Boyle, S.H.; Hellegers, C.; Cheng, H.; Burke, J.R. Metabolomics in early Alzheimer ’ s disease: Identification of altered plasma sphingolipidome using shotgun lipidomics. PLoS One, 2011, 6(7), e21643.
[http://dx.doi.org/10.1371/journal.pone.0021643]
[68]
Mielke, M.M.; Bandaru, V.V.R.; Haughey, N.J.; Rabins, P.V.; Lyketsos, C.G.; Carlson, M.C. Serum sphingomyelins and ceramides are early predictors of memory impairment. Neurobiol. Aging, 2010, 31(1), 17-24.
[http://dx.doi.org/10.1016/j.neurobiolaging.2008.03.011]
[69]
Mielke, M.M.; Haughey, N.J.; Bandaru, V.V.R.; Weinberg, D.D.; Darby, E.; Zaidi, N.; Pavlik, V.; Doody, R.S.; Lyketsos, C.G. Plasma sphingomyelins are associated with cognitive progression in Alzheimer’s disease. J. Alzheimers Dis., 2011, 27(2), 259-269.
[http://dx.doi.org/10.3233/JAD-2011-110405] [PMID: 21841258]
[70]
Chew, H.; Solomon, V.A.; Fonteh, A.N.; Martins, I.J. Involvement of lipids in Alzheimer ’ s Disease pathology and potential therapies the importance of cellular lipid membranes. Front. Physiol., 2020, 11(June), 1-28.
[71]
Mufson, E.J.; Leurgans, S. Inability of plasma and urine F2A-isoprostane levels to differentiate mild cognitive impairment from Alz-heimer’s disease. Neurodegen. Dis, 2010, 139-142.
[72]
Sundelöf, J.; Kilander, L.; Helmersson, J.; Larsson, A.; Rönnemaa, E.; Degerman-Gunnarsson, M.; Sjögren, P.; Basun, H.; Lannfelt, L.; Basu, S. Systemic tocopherols and F2-isoprostanes and the risk of Alzheimer’s disease and dementia: a prospective population-based study. J. Alzheimers Dis., 2009, 18(1), 71-78.
[http://dx.doi.org/10.3233/JAD-2009-1125] [PMID: 19542632]
[73]
Peña-bautista, C.; Durand, T.; Oger, C.; Baquero, M.; Vento, M.; Cháfer-pericás, C. Assessment of lipid peroxidation and artificial neural network models in early Alzheimer disease diagnosis. Clin. Biochem., 2019, 72, 64-70.
[http://dx.doi.org/10.1016/j.clinbiochem.2019.07.008]
[74]
Peña-Bautista, C.; López-Cuevas, R.; Cuevas, A.; Baquero, M.; Cháfer-Pericás, C. Lipid peroxidation biomarkers correlation with medial temporal atrophy in early Alzheimer Disease. Neurochem. Int., 2019, 129, 104519.
[http://dx.doi.org/10.1016/j.neuint.2019.104519] [PMID: 31398364]
[75]
Yoshida, Y.; Yoshikawa, A.; Kinumi, T.; Ogawa, Y.; Saito, Y.; Ohara, K.; Yamamoto, H.; Imai, Y.; Niki, E. Hydroxyoctadecadienoic acid and oxidatively modified peroxiredoxins in the blood of Alzheimer’s disease patients and their potential as biomarkers. Neurobiol. Aging, 2009, 30(2), 174-185.
[http://dx.doi.org/10.1016/j.neurobiolaging.2007.06.012] [PMID: 17688973]
[76]
Casanova, R.; Varma, S.; Simpson, B.; Kim, M.; An, Y.; Saldana, S.; Riveros, C.; Moscato, P.; Griswold, M.; Sonntag, D.; Wahrheit, J.; Klavins, K.; Jonsson, P.V.; Eiriksdottir, G.; Aspelund, T.; Launer, L.J.; Gudnason, V.; Legido Quigley, C.; Thambisetty, M. Blood me-tabolite markers of preclinical Alzheimer’s disease in two longitudinally followed cohorts of older individuals. Alzheimers Dement., 2016, 12(7), 815-822.
[http://dx.doi.org/10.1016/j.jalz.2015.12.008] [PMID: 26806385]
[77]
Orešič, M.; Hyötyläinen, T.; Herukka, S.K.; Sysi-Aho, M.; Mattila, I.; Seppänan-Laakso, T.; Julkunen, V.; Gopalacharyulu, P.V.; Hal-likainen, M.; Koikkalainen, J.; Kivipelto, M.; Helisalmi, S.; Lötjönen, J.; Soininen, H. Metabolome in progression to Alzheimer’s disease. Transl. Psychiatry, 2011, 1(12), e57-e57.
[http://dx.doi.org/10.1038/tp.2011.55] [PMID: 22832349]
[78]
Fiandaca, M.S.; Zhong, X.; Cheema, A.K.; Orquiza, M.H.; Chidambaram, S.; Tan, M.T. Plasma 24-metabolite panel predicts preclinical transition to clinical stages of Alzheimer’s disease. Front. Neurol., 2015, 6, 12.
[79]
Toledo, J.B.; Arnold, M.; Kastenmüller, G.; Chang, R.; Baillie, R.A.; Han, X.; Thambisetty, M.; Tenenbaum, J.D.; Suhre, K.; Thompson, J.W.; John-Williams, L.S.; Mahmoudian, D.S.; Rotroff, D.M.; Jack, J.R.; Motsinger-Reif, A.; Risacher, S.L.; Blach, C.; Lucas, J.E.; Massa-ro, T.; Louie, G.; Zhu, H.; Dallmann, G.; Klavins, K.; Koal, T.; Kim, S.; Nho, K.; Shen, L.; Casanova, R.; Varma, S.; Legido-Quigley, C.; Moseley, M.A.; Zhu, K.; Henrion, M.Y.R.; van der Lee, S.J.; Harms, A.C.; Demirkan, A.; Hankemeier, T.; van Duijn, C.M.; Trojanowski, J.Q.; Shaw, L.M.; Saykin, A.J.; Weiner, M.W.; Doraiswamy, P.M.; Kaddurah-Daouk, R. Metabolic network failures in Alzheimer’s dis-ease: A biochemical road map. Alzheimers Dement., 2017, 13(9), 965-984.
[http://dx.doi.org/10.1016/j.jalz.2017.01.020] [PMID: 28341160]
[80]
McKhann, G.; Drachman, D.; Folstein, M.; Katzman, R.; Price, D.; Stadlan, E.M. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer’s disease. Neurology, 1984, 34(7), 939-944.
[http://dx.doi.org/10.1212/WNL.34.7.939] [PMID: 6610841]
[81]
Folstein, M.F.; Folstein, S.E.; McHugh, P.R. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clini-cian. J. Psychiatr. Res., 1975, 12(3), 189-198.
[http://dx.doi.org/10.1016/0022-3956(75)90026-6] [PMID: 1202204]
[82]
Mohs, R.C.; Knopman, D.; Petersen, R.C.; Ferris, S.H.; Ernesto, C.; Grundman, M.; Sano, M.; Bieliauskas, L.; Geldmacher, D.; Clark, C.; Thal, L.J. Development of cognitive instruments for use in clinical trials of antidementia drugs: additions to the Alzheimer’s Disease As-sessment Scale that broaden its scope. Alzheimer Dis. Assoc. Disord., 1997, 11(Suppl. 2), 13-21.
[83]
Hughes, C.P.; Berg, L.; Danziger, W.L.; Coben, L.A.; Martin, R.L. A new clinical scale for the staging of dementia. Br. J. Psychiatry, 1982, 140(6), 566-572.
[http://dx.doi.org/10.1192/bjp.140.6.566] [PMID: 7104545]
[84]
Frisoni, G.B.; Fox, N.C.; Jack, C.R., Jr; Scheltens, P.; Thompson, P.M. The clinical use of structural MRI in Alzheimer disease. Nat. Rev. Neurol., 2010, 6(2), 67-77.
[http://dx.doi.org/10.1038/nrneurol.2009.215] [PMID: 20139996]
[85]
Nordberg, A.; Rinne, J.O.; Kadir, A.; Långström, B. The use of PET in Alzheimer disease. Nat. Rev. Neurol., 2010, 6(2), 78-87.
[http://dx.doi.org/10.1038/nrneurol.2009.217] [PMID: 20139997]
[86]
Anoop, A.; Singh, P.K.; Jacob, R.S.; Maji, S.K. CSF biomarkers for Alzheimer’s disease diagnosis. Int. J. Alzheimers Dis., 2010, 2010
[http://dx.doi.org/10.4061/2010/606802]
[87]
Blennow, K.; Dubois, B.; Fagan, A.M.; Lewczuk, P.; de Leon, M.J.; Hampel, H. Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer’s disease. Alzheimers Dement., 2015, 11(1), 58-69.
[http://dx.doi.org/10.1016/j.jalz.2014.02.004] [PMID: 24795085]

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