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Current Neuropharmacology

Editor-in-Chief

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

Review Article

Alzheimer’s Disorder: Epigenetic Connection and Associated Risk Factors

Author(s): Vivek Kumar Sharma, Vineet Mehta and Thakur Gurjeet Singh*

Volume 18, Issue 8, 2020

Page: [740 - 753] Pages: 14

DOI: 10.2174/1570159X18666200128125641

Price: $65

Abstract

The gene based therapeutics and drug targets have shown incredible and appreciable advances in alleviating human sufferings and complexities. Epigenetics simply means above genetics or which controls the organism beyond genetics. At present it is very clear that all characteristics of an individual are not determined by DNA alone, rather the environment, stress, life style and nutrition play a vital part in determining the response of an organism. Thus, nature (genetic makeup) and nurture (exposure) play equally important roles in the responses observed, both at the cellular and organism levels. Epigenetics influence plethora of complications at cellular and molecular levels that includes cancer, metabolic and cardiovascular complications including neurological (psychosis) and neurodegenerative disorders (Alzheimer’s disease, Parkinson disease etc.). The epigenetic mechanisms include DNA methylation, histone modification and non coding RNA which have substantial impact on progression and pathways linked to Alzheimer’s disease. The epigenetic mechanism gets deregulated in Alzheimer’s disease and is characterized by DNA hyper methylation, deacetylation of histones and general repressed chromatin state which alter gene expression at the transcription level by upregulation, downregulation or silencing of genes. Thus, the processes or modulators of these epigenetic processes have shown vast potential as a therapeutic target in Alzheimer’s disease.

Keywords: Alzheimer`s disease, epigenetics, amyloid β, DNA methylation, histone, non coding RNA.

Graphical Abstract

[1]
Lane, C.A.H.J.; Hardy, J.; Schott, J.M. Alzheimer’s disease. Eur. J. Neurol., 2018, 25(1), 59-70.
[http://dx.doi.org/10.1111/ene.13439] [PMID: 28872215]
[2]
Vlassenko, A.G.; Benzinger, T.L.; Morris, J.C. PET amyloid-beta imaging in preclinical Alzheimer’s disease. Biochim. Biophys. Acta, 2012, 1822(3), 370-379.
[http://dx.doi.org/10.1016/j.bbadis.2011.11.005] [PMID: 22108203]
[3]
Alzheimer’s Association Report 2019 Alzheimer’s disease facts and figures.,, 15, 321-387.
[4]
Burns, A.; Iliffe, S. Alzheimer’s disease. BMJ, 2009, 338, b158.
[http://dx.doi.org/10.1136/bmj.b158] [PMID: 19196745]
[5]
Querfurth, H.W.; LaFerla, F.M. Alzheimer’s disease. N. Engl. J. Med., 2010, 362(4), 329-344.
[http://dx.doi.org/10.1056/NEJMra0909142] [PMID: 20107219]
[6]
Todd, S.; Barr, S.; Roberts, M.; Passmore, A.P. Survival in dementia and predictors of mortality: a review. Int. J. Geriatr. Psychiatry, 2013, 28(11), 1109-1124.
[http://dx.doi.org/10.1002/gps.3946] [PMID: 23526458]
[7]
Ballard, C.; Gauthier, S.; Corbett, A.; Brayne, C.; Aarsland, D.; Jones, E. Alzheimer’s disease. Lancet, 2011, 377(9770), 1019-1031.
[http://dx.doi.org/10.1016/S0140-6736(10)61349-9] [PMID: 21371747]
[8]
Pimenova, A.A.; Raj, T.; Goate, A.M. Untangling genetic risk for Alzheimer’s Disease. Biol. Psychiatry, 2018, 83(4), 300-310.
[http://dx.doi.org/10.1016/j.biopsych.2017.05.014] [PMID: 28666525]
[9]
Tanzi, R.E. The genetics of Alzheimer disease. Cold Spring Harb. Perspect. Med., 2012, 2(10), 2.
[http://dx.doi.org/10.1101/cshperspect.a006296] [PMID: 23028126]
[10]
Killin, L.O.; Starr, J.M.; Shiue, I.J.; Russ, T.C. Environmental risk factors for dementia: a systematic review. BMC Geriatr., 2016, 16(1), 175.
[http://dx.doi.org/10.1186/s12877-016-0342-y] [PMID: 27729011]
[11]
Migliore, L.; Coppedè, F. Genetics, environmental factors and the emerging role of epigenetics in neurodegenerative diseases. Mutat. Res., 2009, 667(1-2), 82-97.
[http://dx.doi.org/10.1016/j.mrfmmm.2008.10.011] [PMID: 19026668]
[12]
Van Bulck, M.; Sierra-Magro, A.; Alarcon-Gil, J.; Perez-Castillo, A.; Morales-Garcia, J.A. Novel Approaches for the treatment of Alzheimer’s and Parkinson’s Disease. Int. J. Mol. Sci., 2019, 20(3), 719.
[http://dx.doi.org/10.3390/ijms20030719] [PMID: 30743990]
[13]
Lindsley, C.W. Alzheimer’s disease: development of disease-modifying treatments is the challenge for our generation. ACS Chem. Neurosci., 2012, 3(11), 804-805.
[http://dx.doi.org/10.1021/cn300190f] [PMID: 23173063]
[14]
Mitra, S.; Behbahani, H.; Eriksdotter, M. Innovative Therapy for Alzheimer’s Disease-With Focus on Biodelivery of NGF. Front. Neurosci., 2019, 13, 38.
[http://dx.doi.org/10.3389/fnins.2019.00038] [PMID: 30804738]
[15]
Feil, R.; Fraga, M.F. Epigenetics and the environment: emerging patterns and implications. Nat. Rev. Genet., 2012, 13(2), 97-109.
[http://dx.doi.org/10.1038/nrg3142] [PMID: 22215131]
[16]
Mirbahai, L.; Chipman, J.K. Epigenetic memory of environmental organisms: a reflection of lifetime stressor exposures. Mutat. Res. Genet. Toxicol. Environ. Mutagen., 2014, 764-765, 10-17.
[http://dx.doi.org/10.1016/j.mrgentox.2013.10.003] [PMID: 24141178]
[17]
Fuke, C.; Shimabukuro, M.; Petronis, A.; Sugimoto, J.; Oda, T.; Miura, K.; Miyazaki, T.; Ogura, C.; Okazaki, Y.; Jinno, Y. Age related changes in 5-methylcytosine content in human peripheral leukocytes and placentas: an HPLC-based study. Ann. Hum. Genet., 2004, 68(Pt 3), 196-204.
[http://dx.doi.org/10.1046/j.1529-8817.2004.00081.x] [PMID: 15180700]
[18]
Mastroeni, D.; Grover, A.; Delvaux, E.; Whiteside, C.; Coleman, P.D.; Rogers, J. Epigenetic changes in Alzheimer’s disease: decrements in DNA methylation. Neurobiol. Aging, 2010, 31(12), 2025-2037.
[http://dx.doi.org/10.1016/j.neurobiolaging.2008.12.005] [PMID: 19117641]
[19]
Vanyushin, B.F.; Nemirovsky, L.E.; Klimenko, V.V.; Vasiliev, V.K.; Belozersky, A.N. The 5-methylcytosine in DNA of rats. Tissue and age specificity and the changes induced by hydrocortisone and other agents. Gerontologia, 1973, 19(3), 138-152.
[http://dx.doi.org/10.1159/000211967] [PMID: 4763637]
[20]
Wilson, V.L.; Smith, R.A.; Ma, S.; Cutler, R.G. Genomic 5-methyldeoxycytidine decreases with age. J. Biol. Chem., 1987, 262, 9948-9951.
[21]
Moore, L.D.; Le, T.; Fan, G. methylation and its basic function. Neuropsychopharmacology, 2013, 38, 23-38.
[22]
Christopher, M.A.; Kyle, S.M.; Katz, D.J. Neuroepigenetic mechanisms in disease. Epigenetics Chromatin, 2017, 10(1), 47.
[http://dx.doi.org/10.1186/s13072-017-0150-4] [PMID: 29037228]
[23]
Zampieri, M.; Ciccarone, F.; Calabrese, R.; Franceschi, C.; Burkle, A.; Caiafa, P. Reconfiguration of DNA methylation in aging. Mech. Ageing Dev., 2015, 151, 60-70.
[24]
Cheng, Y.; Bernstein, A.; Chen, D.; Jin, P. 5-Hydroxymethylcytosine: A new player in brain disorders? Exp. Neurol., 2015, 268, 3-9.
[http://dx.doi.org/10.1016/j.expneurol.2014.05.008] [PMID: 24845851]
[25]
West, R.L.; Lee, J.M.; Maroun, L.E. Hypomethylation of the amyloid precursor protein gene in the brain of an Alzheimer’s disease patient. J. Mol. Neurosci., 1995, 6(2), 141-146.
[http://dx.doi.org/10.1007/BF02736773] [PMID: 8746452]
[26]
Eid, A.; Bihaqi, S.W.; Renehan, W.E.; Zawia, N.H. Developmental lead exposure and lifespan alterations in epigenetic regulators and their correspondence to biomarkers of Alzheimer’s disease. Alzheimers Dement. (Amst.), 2016, 2, 123-131.
[http://dx.doi.org/10.1016/j.dadm.2016.02.002] [PMID: 27239543]
[27]
Fuso, A.; Seminara, L.; Cavallaro, R.A.; D’Anselmi, F.; Scarpa, S. S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production. Mol. Cell. Neurosci., 2005, 28(1), 195-204.
[http://dx.doi.org/10.1016/j.mcn.2004.09.007] [PMID: 15607954]
[28]
Wu, J.; Basha, M.R.; Brock, B.; Cox, D.P.; Cardozo-Pelaez, F.; McPherson, C.A.; Harry, J.; Rice, D.C.; Maloney, B.; Chen, D.; Lahiri, D.K.; Zawia, N.H. Alzheimer’s disease (AD)-like pathology in aged monkeys after infantile exposure to environmental metal lead (Pb): evidence for a developmental origin and environmental link for AD. J. Neurosci., 2008, 28(1), 3-9.
[http://dx.doi.org/10.1523/JNEUROSCI.4405-07.2008] [PMID: 18171917]
[29]
Bradley-Whitman, M.A.; Lovell, M.A. Epigenetic changes in the progression of Alzheimer’s disease. Mech. Ageing Dev., 2013, 134(10), 486-495.
[http://dx.doi.org/10.1016/j.mad.2013.08.005] [PMID: 24012631]
[30]
Chouliaras, L.; Mastroeni, D.; Delvaux, E.; Grover, A.; Kenis, G.; Hof, P.R.; Steinbusch, H.W.; Coleman, P.D.; Rutten, B.P.; van den Hove, D.L. Consistent decrease in global DNA methylation and hydroxymethylation in the hippocampus of Alzheimer’s disease patients. Neurobiol. Aging, 2013, 34(9), 2091-2099.
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.02.021] [PMID: 23582657]
[31]
Condliffe, D.; Wong, A.; Troakes, C.; Proitsi, P.; Patel, Y.; Chouliaras, L.; Fernandes, C.; Cooper, J.; Lovestone, S.; Schalkwyk, L.; Mill, J.; Lunnon, K. Cross-region reduction in 5-hydroxymethylcytosine in Alzheimer’s disease brain. Neurobiol. Aging, 2014, 35(8), 1850-1854.
[http://dx.doi.org/10.1016/j.neurobiolaging.2014.02.002] [PMID: 24679604]
[32]
Coppieters, N.; Dieriks, B.V.; Lill, C.; Faull, R.L.; Curtis, M.A.; Dragunow, M. Global changes in DNA methylation and hydroxymethylation in Alzheimer’s disease human brain. Neurobiol. Aging, 2014, 35(6), 1334-1344.
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.11.031] [PMID: 24387984]
[33]
Di Francesco, A.; Arosio, B.; Falconi, A.; Micioni Di Bonaventura, M.V.; Karimi, M.; Mari, D.; Casati, M.; Maccarrone, M.; D’Addario, C. Global changes in DNA methylation in Alzheimer’s disease peripheral blood mononuclear cells. Brain Behav. Immun., 2015, 45, 139-144.
[http://dx.doi.org/10.1016/j.bbi.2014.11.002] [PMID: 25452147]
[34]
Hernández, H.G.; Mahecha, M.F.; Mejía, A.; Arboleda, H.; Forero, D.A. Global long interspersed nuclear element 1 DNA methylation in a Colombian sample of patients with late-onset Alzheimer’s disease. Am. J. Alzheimers Dis. Other Demen., 2014, 29(1), 50-53.
[http://dx.doi.org/10.1177/1533317513505132] [PMID: 24164934]
[35]
Lashley, T.; Gami, P.; Valizadeh, N.; Li, A.; Revesz, T.; Balazs, R. Alterations in global DNA methylation and hydroxymethylation are not detected in Alzheimer’s disease. Neuropathol. Appl. Neurobiol., 2015, 41(4), 497-506.
[http://dx.doi.org/10.1111/nan.12183] [PMID: 25201696]
[36]
Mastroeni, D.; McKee, A.; Grover, A.; Rogers, J.; Coleman, P.D. Epigenetic differences in cortical neurons from a pair of monozygotic twins discordant for Alzheimer’s disease. PLoS One, 2009, 4(8), e6617.
[http://dx.doi.org/10.1371/journal.pone.0006617] [PMID: 19672297]
[37]
Ellison, E.M.; Abner, E.L.; Lovell, M.A. Multiregional analysis of global 5-methylcytosine and 5-hydroxymethylcytosine throughout the progression of Alzheimer’s disease. J. Neurochem., 2017, 140(3), 383-394.
[http://dx.doi.org/10.1111/jnc.13912] [PMID: 27889911]
[38]
Barrachina, M.; Ferrer, I. DNA methylation of Alzheimer disease and tauopathy-related genes in postmortem brain. J. Neuropathol. Exp. Neurol., 2009, 68(8), 880-891.
[http://dx.doi.org/10.1097/NEN.0b013e3181af2e46] [PMID: 19606065]
[39]
Corder, E.H.; Saunders, A.M.; Strittmatter, W.J.; Schmechel, D.E.; Gaskell, P.C.; Small, G.W.; Roses, A.D.; Haines, J.L.; Pericak-Vance, M.A. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science, 1993, 261(5123), 921-923.
[http://dx.doi.org/10.1126/science.8346443] [PMID: 8346443]
[40]
Iwata, A.; Nagata, K.; Hatsuta, H.; Takuma, H.; Bundo, M.; Iwamoto, K.; Tamaoka, A.; Murayama, S.; Saido, T.; Tsuji, S. Altered CpG methylation in sporadic Alzheimer’s disease is associated with APP and MAPT dysregulation. Hum. Mol. Genet., 2014, 23(3), 648-656.
[http://dx.doi.org/10.1093/hmg/ddt451] [PMID: 24101602]
[41]
Wang, S.C.; Oelze, B.; Schumacher, A. Age-specific epigenetic drift in late-onset Alzheimer’s disease. PLoS One, 2008, 3(7), e2698.
[http://dx.doi.org/10.1371/journal.pone.0002698] [PMID: 18628954]
[42]
Piaceri, I.; Raspanti, B.; Tedde, A.; Bagnoli, S.; Sorbi, S.; Nacmias, B. Epigenetic modifications in Alzheimer’s disease: cause or effect? J. Alzheimers Dis., 2015, 43(4), 1169-1173.
[http://dx.doi.org/10.3233/JAD-141452] [PMID: 25159670]
[43]
Tannorella, P.; Stoccoro, A.; Tognoni, G.; Petrozzi, L.; Salluzzo, M.G.; Ragalmuto, A.; Siciliano, G.; Haslberger, A.; Bosco, P.; Bonuccelli, U.; Migliore, L.; Coppedè, F. Methylation analysis of multiple genes in blood DNA of Alzheimer’s disease and healthy individuals. Neurosci. Lett., 2015, 600, 143-147.
[http://dx.doi.org/10.1016/j.neulet.2015.06.009] [PMID: 26079324]
[44]
Humphries, C.; Kohli, M.A.; Whitehead, P.; Mash, D.C.; Pericak-Vance, M.A.; Gilbert, J. Alzheimer disease (AD) specific transcription, DNA methylation and splicing in twenty AD associated loci. Mol. Cell. Neurosci., 2015, 67(67), 37-45.
[http://dx.doi.org/10.1016/j.mcn.2015.05.003] [PMID: 26004081]
[45]
Sanchez-Mut, J.V.; Aso, E.; Panayotis, N.; Lott, I.; Dierssen, M.; Rabano, A.; Urdinguio, R.G.; Fernandez, A.F.; Astudillo, A.; Martin-Subero, J.I.; Balint, B.; Fraga, M.F.; Gomez, A.; Gurnot, C.; Roux, J.C.; Avila, J.; Hensch, I.; Ferrer, T.K.; Esteller, M. DNA methylation map of mouse and human brain identifies target genes in Alzheimer’s disease. Brain, 2013, 136, 3018-3027.
[46]
Yu, L.; Chibnik, L.B.; Srivastava, G.P.; Pochet, N.; Yang, J.; Xu, J.; Kozubek, J.; Obholzer, N.; Leurgans, S.E.; Schneider, J.A.; Meissner, A.; De Jager, P.L.; Bennett, D.A. Association of Brain DNA methylation in SORL1, ABCA7, HLA-DRB5, SLC24A4, and BIN1 with pathological diagnosis of Alzheimer disease. JAMA Neurol., 2015, 72(1), 15-24.
[http://dx.doi.org/10.1001/jamaneurol.2014.3049] [PMID: 25365775]
[47]
Fransquet, P.D.; Lacaze, P.; Saffery, R.; McNeil, J.; Woods, R.; Ryan, J. Blood DNA methylation as a potential biomarker of dementia: A systematic review. Alzheimers Dement., 2018, 14(1), 81-103.
[http://dx.doi.org/10.1016/j.jalz.2017.10.002] [PMID: 29127806]
[48]
Wen, K.X.; Miliç, J.; El-Khodor, B.; Dhana, K.; Nano, J.; Pulido, T.; Kraja, B.; Zaciragic, A.; Bramer, W.M.; Troup, J.; Chowdhury, R.; Ikram, M.A.; Dehghan, A.; Muka, T.; Franco, O.H. The role of DNA methylation and histone modifications in neurodegenerative diseases: A systematic review. PLoS One, 2016, 11(12), e0167201.
[http://dx.doi.org/10.1371/journal.pone.0167201] [PMID: 27973581]
[49]
Celarain, N.; Sánchez-Ruiz de Gordoa, J.; Zelaya, M.V.; Roldán, M.; Larumbe, R.; Pulido, L.; Echavarri, C.; Mendioroz, M. TREM2 upregulation correlates with 5-hydroxymethycytosine enrichment in Alzheimer’s disease hippocampus. Clin. Epigenetics, 2016, 8, 37.
[http://dx.doi.org/10.1186/s13148-016-0202-9] [PMID: 27051467]
[50]
Nagata, T.; Kobayashi, N.; Ishii, J.; Shinagawa, S.; Nakayama, R.; Shibata, N.; Kuerban, B.; Ohnuma, T.; Kondo, K.; Arai, H.; Yamada, H.; Nakayama, K. Association between DNA methylation of the BDNF promoter region and clinical presentation in Alzheimer’s Disease. Dement. Geriatr. Cogn. Disord. Extra, 2015, 5(1), 64-73.
[http://dx.doi.org/10.1159/000375367] [PMID: 25873928]
[51]
Ozaki, Y.; Yoshino, Y.; Yamazaki, K.; Sao, T.; Mori, Y.; Ochi, S.; Yoshida, T.; Mori, T.; Iga, J.I.; Ueno, S.I. DNA methylation changes at TREM2 intron 1 and TREM2 mRNA expression in patients with Alzheimer’s disease. J. Psychiatr. Res., 2017, 92, 74-80.
[http://dx.doi.org/10.1016/j.jpsychires.2017.04.003] [PMID: 28412600]
[52]
Rao, J.S.; Keleshian, V.L.; Klein, S.; Rapoport, S.I. Epigenetic modifications in frontal cortex from Alzheimer’s disease and bipolar disorder patients. Transl. Psychiatry, 2012, 2, e132.
[http://dx.doi.org/10.1038/tp.2012.55] [PMID: 22760556]
[53]
Smith.; A.R.; Smith, R.G.; Condliffe, D.; Hannon, E.; Schalkwyk, L.; Mill, J.; Lunnon, K. Increased DNA methylation near TREM2 is consistently seen in the superior temporal gyrus in Alzheimer’s disease brain. Neurobiol. Aging, 2016, 47, 35-40.
[http://dx.doi.org/10.1016/j.neurobiolaging.2016.07.008]
[54]
Xie, B.; Liu, Z.; Liu, W.; Jiang, L.; Zhang, R.; Cui, D.; Zhang, Q.; Xu, S. DNA Methylation and Tag SNPs of the BDNF gene in conversion of amnestic mild cognitive impairment into Alzheimer’s disease: A Cross-Sectional Cohort Study. J. Alzheimers Dis., 2017a, 58(1), 263-274.
[http://dx.doi.org/10.3233/JAD-170007] [PMID: 28387675]
[55]
Xie, B.; Xu, Y.; Liu, Z.; Liu, W.; Jiang, L.; Zhang, R.; Cui, D.; Zhang, Q.; Xu, S. Elevation of peripheral BDNF promoter methylation predicts conversion from amnestic mild cognitive impairment to Alzheimer’s Disease: A 5-Year longitudinal study. J. Alzheimers Dis., 2017b, 56(1), 391-401.
[http://dx.doi.org/10.3233/JAD-160954] [PMID: 27935556]
[56]
Irier, H.A.; Jin, P. Dynamics of DNA methylation in aging and Alzheimer’s disease. DNA Cell Biol., 2012, 31(1)(Suppl. 1), S42-S48.
[http://dx.doi.org/10.1089/dna.2011.1565] [PMID: 22313030]
[57]
Song, C.X.; Szulwach, K.E.; Fu, Y.; Dai, Q.; Yi, C.; Li, X.; Li, Y.; Chen, C.H.; Zhang, W.; Jian, X.; Wang, J.; Zhang, L.; Looney, T.J.; Zhang, B.; Godley, L.A.; Hicks, L.M.; Lahn, B.T.; Jin, P.; He, C. Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine. Nat. Biotechnol., 2011, 29(1), 68-72.
[http://dx.doi.org/10.1038/nbt.1732] [PMID: 21151123]
[58]
Bakulski, K.M.; Dolinoy, D.C.; Sartor, M.A.; Paulson, H.L.; Konen, J.R.; Lieberman, A.P.; Albin, R.L.; Hu, H.; Rozek, L.S. Genome-wide DNA methylation differences between late-onset Alzheimer’s disease and cognitively normal controls in human frontal cortex. J. Alzheimers Dis., 2012, 29(3), 571-588.
[http://dx.doi.org/10.3233/JAD-2012-111223] [PMID: 22451312]
[59]
Lunnon, K.; Smith, R.; Hannon, E.; De Jager, P.L.; Srivastava, G.; Volta, M.; Troakes, C.; Al-Sarraj, S.; Burrage, J.; Macdonald, R.; Condliffe, D.; Harries, L.W.; Katsel, P.; Haroutunian, V.; Kaminsky, Z.; Joachim, C.; Powell, J.; Lovestone, S.; Bennett, D.A.; Schalkwyk, L.C.; Mill, J. Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer’s disease. Nat. Neurosci., 2014, 17(9), 1164-1170.
[http://dx.doi.org/10.1038/nn.3782] [PMID: 25129077]
[60]
De Jager, P.L.; Srivastava, G.; Lunnon, K.; Burgess, J.; Schalkwyk, L.C.; Yu, L.; Eaton, M.L.; Keenan, B.T.; Ernst, J.; McCabe, C.; Tang, A.; Raj, T.; Replogle, J.; Brodeur, W.; Gabriel, S.; Chai, H.S.; Younkin, C.; Younkin, S.G.; Zou, F.; Szyf, M.; Epstein, C.B.; Schneider, J.A.; Bernstein, B.E.; Meissner, A.; Ertekin-Taner, N.; Chibnik, L.B.; Kellis, M.; Mill, J.; Bennett, D.A. Alzheimer’s disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci. Nat. Neurosci., 2014, 17(9), 1156-1163.
[http://dx.doi.org/10.1038/nn.3786] [PMID: 25129075]
[61]
Roubroeks, J.A.Y.; Smith, R.G.; van den Hove, D.L.A.; Lunnon, K. Epigenetics and DNA methylomic profiling in Alzheimer’s disease and other neurodegenerative diseases. J. Neurochem., 2017, 143(2), 158-170.
[http://dx.doi.org/10.1111/jnc.14148] [PMID: 28805248]
[62]
Watson, C.T.; Roussos, P.; Garg, P.; Ho, D.J.; Azam, N.; Katsel, P.L.; Haroutunian, V.; Sharp, A.J. Genome-wide DNA methylation profiling in the superior temporal gyrus reveals epigenetic signatures associated with Alzheimer’s disease. Genome Med., 2016, 8(1), 5.
[http://dx.doi.org/10.1186/s13073-015-0258-8] [PMID: 26803900]
[63]
Konki, M.; Malonzo, M.; Karlsson, I.; Lindgren, N.; Ghimire, B.; Smolander, J.; Scheinin, N.; Ollikainen, M.; Laiho, A.; Elo, L.L. Peripheral blood DNA methylation differences in twin pairs discordant for Alzheimer’s disease. Clin. Epigenetics, 2019, 11(1), 130.
[64]
Mladenova, D.; Barry, G.; Konen, L.M.; Pineda, S.S.; Guennewig, B.; Avesson, L.; Zinn, R.; Schonrock, N.; Bitar, M.; Jonkhout, N.; Crumlish, L.; Kaczorowski, D.C.; Gong, A.; Pinese, M.; Franco, G.R.; Walkley, C.R.; Vissel, B.; Mattick, J.S. Adar3 is involved in learning and memory in mice. Front. Neurosci., 2018, 12, 243.
[http://dx.doi.org/10.3389/fnins.2018.00243] [PMID: 29719497]
[65]
Zhao, J.; Zhu, Y.; Yang, J.; Li, L.; Wu, H.; De Jager, P.L.; Jin, P.; Bennett, D.A. A genome-wide profiling of brain DNA hydroxymethylation in Alzheimer’s disease. Alzheimers Dement., 2017, 13(6), 674-688.
[http://dx.doi.org/10.1016/j.jalz.2016.10.004] [PMID: 28089213]
[66]
Bernstein, A.I.; Lin, Y.; Street, R.C.; Lin, L.; Dai, Q.; Yu, L.; Bao, H.; Gearing, M.; Lah, J.J.; Nelson, P.T.; He, C.; Levey, A.I.; Mullé, J.G.; Duan, R.; Jin, P. 5-Hydroxymethylation-associated epigenetic modifiers of Alzheimer’s disease modulate Tau-induced neurotoxicity. Hum. Mol. Genet., 2016, 25(12), 2437-2450.
[http://dx.doi.org/10.1093/hmg/ddw109] [PMID: 27060332]
[67]
Mposhi, A.; Van der Wijst, M.G.; Faber, K.N.; Rots, M.G. Regulation of mitochondrial gene expression, the epigenetic enigma. Front. Biosci., 2017, 22, 1099-1113.
[http://dx.doi.org/10.2741/4535] [PMID: 28199194]
[68]
Hroudová, J.; Singh, N.; Fišar, Z. Mitochondrial dysfunctions in neurodegenerative diseases: relevance to Alzheimer’s disease. BioMed Res. Int., 2014, 2014, 175062.
[http://dx.doi.org/10.1155/2014/175062] [PMID: 24900954]
[69]
Stoccoro, A.; Siciliano, G.; Migliore, L.; Coppedè, F. Decreased methylation of the mitochondrial d-loop region in late-onset Alzheimer’s Disease. J. Alzheimers Dis., 2017, 59(2), 559-564.
[http://dx.doi.org/10.3233/JAD-170139] [PMID: 28655136]
[70]
Nagata, K.; Mano, T.; Murayama, S.; Saido, T.C.; Iwata, A. DNA methylation level of the neprilysin promoter in Alzheimer’s disease brains. Neurosci. Lett., 2018, 670, 8-13.
[http://dx.doi.org/10.1016/j.neulet.2018.01.003] [PMID: 29339171]
[71]
Turner, A.J.; Fisk, L.; Nalivaeva, N.N. Targeting amyloid-degrading enzymes as therapeutic strategies in neurodegeneration. Ann. N. Y. Acad. Sci., 2004, 1035, 1-20.
[http://dx.doi.org/10.1196/annals.1332.001] [PMID: 15681797]
[72]
Anderson, K.W.; Turko, I.V. Histone post-translational modifications in frontal cortex from human donors with Alzheimer’s disease. Clin. Proteomics, 2015, 12, 26.
[http://dx.doi.org/10.1186/s12014-015-9098-1] [PMID: 26435705]
[73]
Fischer, A.; Sananbenesi, F.; Mungenast, A.; Tsai, L.H. Targeting the correct HDAC(s) to treat cognitive disorders. Trends Pharmacol. Sci., 2010, 31(12), 605-617.
[http://dx.doi.org/10.1016/j.tips.2010.09.003] [PMID: 20980063]
[74]
Gräff, J.; Rei, D.; Guan, J.S.; Wang, W.Y.; Seo, J.; Hennig, K.M.; Nieland, T.J.; Fass, D.M.; Kao, P.F.; Kahn, M.; Su, S.C.; Samiei, A.; Joseph, N.; Haggarty, S.J.; Delalle, I.; Tsai, L.H. An epigenetic blockade of cognitive functions in the neurodegenerating brain. Nature, 2012, 483(7388), 222-226.
[http://dx.doi.org/10.1038/nature10849] [PMID: 22388814]
[75]
Narayan, P.J.; Lill, C.; Faull, R.; Curtis, M.A.; Dragunow, M. Increased acetyl and total histone levels in post-mortem Alzheimer’s disease brain. Neurobiol. Dis., 2015, 74, 281-294.
[http://dx.doi.org/10.1016/j.nbd.2014.11.023] [PMID: 25484284]
[76]
Zhang, K.; Schrag, M.; Crofton, A.; Trivedi, R.; Vinters, H.; Kirsch, W. Targeted proteomics for quantification of histone acetylation in Alzheimer’s disease. Proteomics, 2012, 12(8), 1261-1268.
[http://dx.doi.org/10.1002/pmic.201200010] [PMID: 22577027]
[77]
Kouskouti, A.; Talianidis, I. Histone modifications defining active genes persist after transcriptional and mitotic inactivation. EMBO J., 2005, 24(2), 347-357.
[http://dx.doi.org/10.1038/sj.emboj.7600516] [PMID: 15616580]
[78]
Bannister, A.J.; Kouzarides, T. Regulation of chromatin by histone modifications. Cell Res., 2011, 21(3), 381-395.
[http://dx.doi.org/10.1038/cr.2011.22] [PMID: 21321607]
[79]
Plagg, B.; Ehrlich, D.; Kniewallner, K.M.; Marksteiner, J.; Humpel, C. Increased acetylation of histone H4 at Lysine 12 (H4K12) in monocytes of transgenic alzheimer’s mice and in human patients. Curr. Alzheimer Res., 2015, 12(8), 752-760.
[http://dx.doi.org/10.2174/1567205012666150710114256] [PMID: 26159193]
[80]
Coppedè, F. The potential of epigenetic therapies in neurodegenerative diseases. Front. Genet., 2014, 5, 220.
[http://dx.doi.org/10.3389/fgene.2014.00220] [PMID: 25071843]
[81]
Sung, Y.M.; Lee, T.; Yoon, H.; DiBattista, A.M.; Song, J.M.; Sohn, Y.; Moffat, E.I.; Turner, R.S.; Jung, M.; Kim, J.; Hoe, H.S. Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer’s disease. Exp. Neurol., 2013, 239, 192-201.
[http://dx.doi.org/10.1016/j.expneurol.2012.10.005] [PMID: 23063601]
[82]
Maoz, R.; Garfinkel, B.P.; Soreq, H. Alzheimer’s Disease and ncRNAs. Adv. Exp. Med. Biol., 2017, 978, 337-361.
[http://dx.doi.org/10.1007/978-3-319-53889-1_18] [PMID: 28523555]
[83]
Peschansky, V.J.; Wahlestedt, C. Non-coding RNAs as direct and indirect modulators of epigenetic regulation. Epigenetics, 2014, 9(1), 3-12.
[http://dx.doi.org/10.4161/epi.27473] [PMID: 24739571]
[84]
Hébert, S.S.; Horré, K.; Nicolaï, L.; Papadopoulou, A.S.; Mandemakers, W.; Silahtaroglu, A.N.; Kauppinen, S.; Delacourte, A.; De Strooper, B. Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer’s disease correlates with increased BACE1/beta-secretase expression. Proc. Natl. Acad. Sci. USA, 2008, 105(17), 6415-6420.
[http://dx.doi.org/10.1073/pnas.0710263105] [PMID: 18434550]
[85]
Lei, X.; Lei, L.; Zhang, Z.; Zhang, Z.; Cheng, Y. Downregulated miR-29c correlates with increased BACE1 expression in sporadic Alzheimer’s disease. Int. J. Clin. Exp. Pathol., 2015, 8(2), 1565-1574.
[PMID: 25973041]
[86]
Yang, G.; Song, Y.; Zhou, X.; Deng, Y.; Liu, T.; Weng, G.; Yu, D.; Pan, S. MicroRNA-29c targets β-site amyloid precursor protein-cleaving enzyme 1 and has a neuroprotective role in vitro and in vivo. Mol. Med. Rep., 2015, 12(2), 3081-3088.
[http://dx.doi.org/10.3892/mmr.2015.3728] [PMID: 25955795]
[87]
Guedes, J.R.; Custódia, C.M.; Silva, R.J.; de Almeida, L.P.; Pedroso de Lima, M.C.; Cardoso, A.L. Early miR-155 upregulation contributes to neuroinflammation in Alzheimer’s disease triple transgenic mouse model. Hum. Mol. Genet., 2014, 23(23), 6286-6301.
[http://dx.doi.org/10.1093/hmg/ddu348] [PMID: 24990149]
[88]
Kim, J.; Yoon, H.; Horie, T.; Burchett, J.M.; Restivo, J.L.; Rotllan, N.; Ramírez, C.M.; Verghese, P.B.; Ihara, M.; Hoe, H.S.; Esau, C.; Fernández-Hernando, C.; Holtzman, D.M.; Cirrito, J.R.; Ono, K.; Kim, J. MicroRNA-33 Regulates ApoE Lipidation and Amyloid-β metabolism in the brain. J. Neurosci., 2015, 35(44), 14717-14726.
[http://dx.doi.org/10.1523/JNEUROSCI.2053-15.2015] [PMID: 26538644]
[89]
Schipper, H.M.; Maes, O.C.; Chertkow, H.M.; Wang, E. MicroRNA expression in Alzheimer blood mononuclear cells. Gene Regul. Syst. Bio., 2007, 1, 263-274.
[http://dx.doi.org/10.4137/GRSB.S361] [PMID: 19936094]
[90]
Ciarlo, E.; Massone, S.; Penna, I.; Nizzari, M.; Gigoni, A.; Dieci, G.; Russo, C.; Florio, T.; Cancedda, R.; Pagano, A. An intronic ncRNA-dependent regulation of SORL1 expression affecting Aβ formation is upregulated in post-mortem Alzheimer’s disease brain samples. Dis. Model. Mech., 2013, 6(2), 424-433.
[http://dx.doi.org/10.1242/dmm.009761] [PMID: 22996644]
[91]
Faghihi, M.A.; Modarresi, F.; Khalil, A.M.; Wood, D.E.; Sahagan, B.G.; Morgan, T.E.; Finch, C.E.; St Laurent, G.; Kenny, P.J.; Wahlestedt, C. Expression of a noncoding RNA is elevated in Alzheimer’s disease and drives rapid feed-forward regulation of beta-secretase. Nat. Med., 2008, 14(7), 723-730.
[PMID: 18587408]
[92]
Magistri, M.; Velmeshev, D.; Makhmutova, M.; Faghihi, M.A. Transcriptomics Profiling of Alzheimer’s Disease reveal neurovascular defects, altered amyloid-β homeostasis, and deregulated expression of long noncoding RNAs. J. Alzheimers Dis., 2015, 48(3), 647-665.
[http://dx.doi.org/10.3233/JAD-150398] [PMID: 26402107]
[93]
Massone, S.; Vassallo, I.; Fiorino, G.; Castelnuovo, M.; Barbieri, F.; Borghi, R.; Tabaton, M.; Robello, M.; Gatta, E.; Russo, C.; Florio, T.; Dieci, G.; Cancedda, R.; Pagano, A. 17A, a novel non-coding RNA, regulates GABA B alternative splicing and signaling in response to inflammatory stimuli and in Alzheimer disease. Neurobiol. Dis., 2011, 41(2), 308-317.
[http://dx.doi.org/10.1016/j.nbd.2010.09.019] [PMID: 20888417]
[94]
Mus, E.; Hof, P.R.; Tiedge, H. Dendritic BC200 RNA in aging and in Alzheimer’s disease. Proc. Natl. Acad. Sci. USA, 2007, 104(25), 10679-10684.
[http://dx.doi.org/10.1073/pnas.0701532104] [PMID: 17553964]
[95]
Scheckel, C.; Drapeau, E.; Frias, M.A.; Park, C.Y.; Fak, J.; Zucker-Scharff, I.; Kou, Y.; Haroutunian, V.; Ma’ayan, A.; Buxbaum, J.D.; Darnell, R.B. Regulatory consequences of neuronal ELAV-like protein binding to coding and non-coding RNAs in human brain. eLife, 2016, 5, 5.
[http://dx.doi.org/10.7554/eLife.10421] [PMID: 26894958]
[96]
Zhou, X.; Xu, J. Identification of Alzheimer’s disease-associated long noncoding RNAs. Neurobiol. Aging, 2015, 36(11), 2925-2931.
[http://dx.doi.org/10.1016/j.neurobiolaging.2015.07.015] [PMID: 26318290]
[97]
Alonso, A.; Zaidi, T.; Novak, M.; Grundke-Iqbal, I.; Iqbal, K. Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments. Proc. Natl. Acad. Sci. USA, 2001, 98(12), 6923-6928.
[http://dx.doi.org/10.1073/pnas.121119298] [PMID: 11381127]
[98]
Lovestone, S.; Reynolds, C.H. The phosphorylation of tau: a critical stage in neurodevelopment and neurodegenerative processes. Neuroscience, 1997, 78(2), 309-324.
[PMID: 9145789]
[99]
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]
[100]
Tohgi, H.; Utsugisawa, K.; Nagane, Y.; Yoshimura, M.; Ukitsu, M.; Genda, Y. The methylation status of cytosines in a tau gene promoter region alters with age to downregulate transcriptional activity in human cerebral cortex. Neurosci. Lett., 1999, 275(2), 89-92.
[http://dx.doi.org/10.1016/S0304-3940(99)00731-4] [PMID: 10568506]
[101]
Sontag, E.; Nunbhakdi-Craig, V.; Sontag, J.M.; Diaz-Arrastia, R.; Ogris, E.; Dayal, S.; Lentz, S.R.; Arning, E.; Bottiglieri, T. Protein phosphatase 2A methyltransferase links homocysteine metabolism with tau and amyloid precursor protein regulation. J. Neurosci., 2007, 27(11), 2751-2759.
[http://dx.doi.org/10.1523/JNEUROSCI.3316-06.2007] [PMID: 17360897]
[102]
Zhang, C.E.; Tian, Q.; Wei, W.; Peng, J.H.; Liu, G.P.; Zhou, X.W.; Wang, Q.; Wang, D.W.; Wang, J.Z. Homocysteine induces tau phosphorylation by inactivating protein phosphatase 2A in rat hippocampus. Neurobiol. Aging, 2008, 29(11), 1654-1665.
[http://dx.doi.org/10.1016/j.neurobiolaging.2007.04.015] [PMID: 17537547]
[103]
Nicolia, V.; Fuso, A.; Cavallaro, R.A.; Di Luzio, A.; Scarpa, S. B vitamin deficiency promotes tau phosphorylation through regulation of GSK3beta and PP2A. J. Alzheimers Dis., 2010, 19(3), 895-907.
[http://dx.doi.org/10.3233/JAD-2010-1284] [PMID: 20157245]
[104]
Popkie, A.P.; Zeidner, L.C.; Albrecht, A.M.; D’Ippolito, A.; Eckardt, S.; Newsom, D.E.; Groden, J.; Doble, B.W.; Aronow, B.; McLaughlin, K.J.; White, P.; Phiel, C.J. Phosphatidylinositol 3-kinase (PI3K) signaling via glycogen synthase kinase-3 (Gsk-3) regulates DNA methylation of imprinted loci. J. Biol. Chem., 2010, 285(53), 41337-41347.
[http://dx.doi.org/10.1074/jbc.M110.170704] [PMID: 21047779]
[105]
Xie, A.; Gao, J.; Xu, L.; Meng, D. Shared mechanisms of neurodegeneration in Alzheimer's disease and Parkinson's disease. BioMed research internationa.,, 2014, 2014 648740.
[106]
Cruickshanks, H.A.; McBryan, T.; Nelson, D.M.; Vanderkraats, N.D.; Shah, P.P.; van Tuyn, J.; Singh Rai, T.; Brock, C.; Donahue, G.; Dunican, D.S.; Drotar, M.E.; Meehan, R.R.; Edwards, J.R.; Berger, S.L.; Adams, P.D. Senescent cells harbour features of the cancer epigenome. Nat. Cell Biol., 2013, 15(12), 1495-1506.
[http://dx.doi.org/10.1038/ncb2879] [PMID: 24270890]
[107]
Salta, E.; Sierksma, A.; Vanden Eynden, E.; De Strooper, B. miR-132 loss de-represses ITPKB and aggravates amyloid and TAU pathology in Alzheimer’s brain. EMBO Mol. Med., 2016, 8(9), 1005-1018.
[http://dx.doi.org/10.15252/emmm.201606520] [PMID: 27485122]
[108]
Zhang, W.; Li, J.; Suzuki, K.; Qu, J.; Wang, P.; Zhou, J.; Liu, X.; Ren, R.; Xu, X.; Ocampo, A.; Yuan, T.; Yang, J.; Li, Y.; Shi, L.; Guan, D.; Pan, H.; Duan, S.; Ding, Z.; Li, M.; Yi, F.; Bai, R.; Wang, Y.; Chen, C.; Yang, F.; Li, X.; Wang, Z.; Aizawa, E.; Goebl, A.; Soligalla, R.D.; Reddy, P.; Esteban, C.R.; Tang, F.; Liu, G.H.; Belmonte, J.C. Aging stem cells. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging. Science, 2015, 348(6239), 1160-1163.
[http://dx.doi.org/10.1126/science.aaa1356] [PMID: 25931448]
[109]
Cheung, I.; Shulha, H.P.; Jiang, Y.; Matevossian, A.; Wang, J.; Weng, Z.; Akbarian, S. Developmental regulation and individual differences of neuronal H3K4me3 epigenomes in the prefrontal cortex. Proc. Natl. Acad. Sci. USA, 2010, 107(19), 8824-8829.
[http://dx.doi.org/10.1073/pnas.1001702107] [PMID: 20421462]
[110]
Liu, L.; Cheung, T.H.; Charville, G.W.; Hurgo, B.M.; Leavitt, T.; Shih, J.; Brunet, A.; Rando, T.A. Chromatin modifications as determinants of muscle stem cell quiescence and chronological aging. Cell Rep., 2013, 4(1), 189-204.
[http://dx.doi.org/10.1016/j.celrep.2013.05.043] [PMID: 23810552]
[111]
Pu, M.; Ni, Z.; Wang, M.; Wang, X.; Wood, J.G.; Helfand, S.L.; Yu, H.; Lee, S.S. Trimethylation of Lys36 on H3 restricts gene expression change during aging and impacts life span. Genes Dev., 2015, 29(7), 718-731.
[http://dx.doi.org/10.1101/gad.254144.114] [PMID: 25838541]
[112]
Numata, S.; Ye, T.; Hyde, T.M.; Guitart-Navarro, X.; Tao, R.; Wininger, M.; Colantuoni, C.; Weinberger, D.R.; Kleinman, J.E.; Lipska, B.K. DNA methylation signatures in development and aging of the human prefrontal cortex. Am. J. Hum. Genet., 2012, 90(2), 260-272.
[http://dx.doi.org/10.1016/j.ajhg.2011.12.020] [PMID: 22305529]
[113]
Klein, H.U.; Bennett, D.A.; De Jager, P.L. The epigenome in Alzheimer’s disease: current state and approaches for a new path to gene discovery and understanding disease mechanism. Acta Neuropathol., 2016, 132(4), 503-514.
[http://dx.doi.org/10.1007/s00401-016-1612-7] [PMID: 27573688]
[114]
Eid, A.; Bihaqi, S.W.; Hemme, C.; Gaspar, J.M.; Hart, R.P.; Zawia, N.H. Histone acetylation maps in aged mice developmentally exposed to lead: epigenetic drift and Alzheimer-related genes. Epigenomics, 2018, 10(5), 573-583.
[http://dx.doi.org/10.2217/epi-2017-0143] [PMID: 29722544]
[115]
McCartney, D.L.; Stevenson, A.J.; Walker, R.M.; Gibson, J.; Morris, S.W.; Campbell, A.; Murray, A.D.; Whalley, H.C.; Porteous, D.J.; McIntosh, A.M.; Evans, K.L.; Deary, I.J.; Marioni, R.E. Investigating the relationship between DNA methylation age acceleration and risk factors for Alzheimer’s disease. Alzheimers Dement. (Amst.), 2018, 10, 429-437.
[http://dx.doi.org/10.1016/j.dadm.2018.05.006] [PMID: 30167451]
[116]
Sato, T.; Cesaroni, M.; Chung, W.; Panjarian, S.; Tran, A.; Madzo, J.; Okamoto, Y.; Zhang, H.; Chen, X.; Jelinek, J.; Issa, J.J. Transcriptional selectivity of epigenetic therapy in cancer. Cancer Res., 2017, 77, 470-481.
[http://dx.doi.org/10.1158/0008-5472.CAN-16-0834] [PMID: 27879268]
[117]
Wang, J.; Yu, J.T.; Tan, M.S.; Jiang, T.; Tan, L. Epigenetic mechanisms in Alzheimer’s disease: implications for pathogenesis and therapy. Ageing Res. Rev., 2013, 12(4), 1024-1041.
[http://dx.doi.org/10.1016/j.arr.2013.05.003] [PMID: 23688931]
[118]
Durga, J.; van Boxtel, M.P.; Schouten, E.G.; Kok, F.J.; Jolles, J.; Katan, M.B.; Verhoef, P. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet, 2007, 369(9557), 208-216.
[http://dx.doi.org/10.1016/S0140-6736(07)60109-3] [PMID: 17240287]
[119]
Haan, M.N.; Miller, J.W.; Aiello, A.E.; Whitmer, R.A.; Jagust, W.J.; Mungas, D.M.; Allen, L.H.; Green, R. Homocysteine, B vitamins, and the incidence of dementia and cognitive impairment: results from the sacramento area latino study on aging. Am. J. Clin. Nutr., 2007, 85(2), 511-517.
[http://dx.doi.org/10.1093/ajcn/85.2.511] [PMID: 17284751]
[120]
Werneke, U.; Turner, T.; Priebe, S. Complementary medicines in psychiatry: review of effectiveness and safety. Br. J. Psychiatry, 2006, 188(188), 109-121.
[http://dx.doi.org/10.1192/bjp.188.2.109] [PMID: 16449696]
[121]
Cao, X.J.; Huang, S.H.; Wang, M.; Chen, J.T.; Ruan, D.Y. S-adenosyl-L-methionine improves impaired hippocampal long-term potentiation and water maze performance induced by developmental lead exposure in rats. Eur. J. Pharmacol., 2008, 595(1-3), 30-34.
[http://dx.doi.org/10.1016/j.ejphar.2008.07.061] [PMID: 18713624]
[122]
Kumar, D.; Aggarwal, M.; Kaas, G.A.; Lewis, J.; Wang, J.; Ross, D.L.; Zhong, C.; Kennedy, A.; Song, H.; Sweatt, J.D. Tet1 oxidase regulates neuronal gene transcription, active dna hydroxy-methylation, object location memory, and threat recognition memory. Neuroepigenetics, 2015, 4, 12-27.
[http://dx.doi.org/10.1016/j.nepig.2015.10.002] [PMID: 26644996]
[123]
Smith, R.G.; Hannon, E.; De Jager, P.L.; Chibnik, L.; Lott, S.J.; Condliffe, D.; Smith, A.R.; Haroutunian, V.; Troakes, C.; Al-Sarraj, S.; Bennett, D.A.; Powell, J.; Lovestone, S.; Schalkwyk, L.; Mill, J.; Lunnon, K. Elevated DNA methylation across a 48-kb region spanning the HOXA gene cluster is associated with Alzheimer’s disease neuropathology. Alzheimers Dement., 2018, 14(12), 1580-1588.
[http://dx.doi.org/10.1016/j.jalz.2018.01.017] [PMID: 29550519]
[124]
Gasparoni, G.; Bultmann, S.; Lutsik, P.; Kraus, T.F.J.; Sordon, S.; Vlcek, J.; Dietinger, V.; Steinmaurer, M.; Haider, M.; Mulholland, C.B.; Arzberger, T.; Roeber, S.; Riemenschneider, M.; Kretzschmar, H.A.; Giese, A.; Leonhardt, H.; Walter, J. DNA methylation analysis on purified neurons and glia dissects age and Alzheimer’s disease-specific changes in the human cortex. Epigenetics Chromatin, 2018, 11(1), 41.
[http://dx.doi.org/10.1186/s13072-018-0211-3] [PMID: 30045751]
[125]
Su, Y.; Ryder, J.; Li, B.; Wu, X.; Fox, N.; Solenberg, P.; Brune, K.; Paul, S.; Zhou, Y.; Liu, F.; Ni, B. Lithium, a common drug for bipolar disorder treatment, regulates amyloid-beta precursor protein processing. Biochemistry, 2004, 43(22), 6899-6908.
[http://dx.doi.org/10.1021/bi035627j] [PMID: 15170327]
[126]
Qing, H.; He, G.; Ly, P.T.; Fox, C.J.; Staufenbiel, M.; Cai, F.; Zhang, Z.; Wei, S.; Sun, X.; Chen, C.H.; Zhou, W.; Wang, K.; Song, W. Valproic acid inhibits Abeta production, neuritic plaque formation, and behavioral deficits in Alzheimer’s disease mouse models. J. Exp. Med., 2008, 205(12), 2781-2789.
[http://dx.doi.org/10.1084/jem.20081588] [PMID: 18955571]
[127]
Ricobaraza, A.; Cuadrado-Tejedor, M.; Marco, S.; Pérez-Otaño, I.; García-Osta, A. Phenylbutyrate rescues dendritic spine loss associated with memory deficits in a mouse model of Alzheimer disease. Hippocampus, 2012, 22(5), 1040-1050.
[http://dx.doi.org/10.1002/hipo.20883] [PMID: 21069780]
[128]
Ricobaraza, A.; Cuadrado-Tejedor, M.; Perez-Mediavilla, A.; Frechilla, D.; Del Rio, J.; Garcia-Osta, A. Phenylbutyrate ameliorates cognitive deficit and reduces tau pathology in an Alzheimer’s disease mouse model. Neuropsychopharmacology, 2009, 34, 1721-1732.
[129]
Peleg, S.; Sananbenesi, F.; Zovoilis, A.; Burkhardt, S.; Bahari-Javan, S.; Agis-Balboa, R.C.; Cota, P.; Wittnam, J.L.; Gogol-Doering, A.; Opitz, L.; Salinas-Riester, G.; Dettenhofer, M.; Kang, H.; Farinelli, L.; Chen, W.; Fischer, A. Altered histone acetylation is associated with age-dependent memory impairment in mice. Science, 2010, 328(5979), 753-756.
[http://dx.doi.org/10.1126/science.1186088] [PMID: 20448184]
[130]
Kilgore, M.; Miller, C.A.; Fass, D.M.; Hennig, K.M.; Haggarty, S.J.; Sweatt, J.D.; Rumbaugh, G. Inhibitors of class 1 histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimer’s disease. Neuropsychopharmacology, 2010, 35, 870-880.
[131]
Green, K.N.; Steffan, J.S.; Martinez-Coria, H.; Sun, X.; Schreiber, S.S.; Thompson, L.M.; LaFerla, F.M. Nicotinamide restores cognition in Alzheimer’s disease transgenic mice via a mechanism involving sirtuin inhibition and selective reduction of Thr231-phosphotau. J. Neurosci., 2008, 28(45), 11500-11510.
[http://dx.doi.org/10.1523/JNEUROSCI.3203-08.2008] [PMID: 18987186]
[132]
Brahe, C.; Vitali, T.; Tiziano, F.D.; Angelozzi, C.; Pinto, A.M.; Borgo, F.; Moscato, U.; Bertini, E.; Mercuri, E.; Neri, G. Phenylbutyrate increases SMN gene expression in spinal muscular atrophy patients. Eur. J. Hum. Genet., 2005, 13(2), 256-259.
[http://dx.doi.org/10.1038/sj.ejhg.5201320] [PMID: 15523494]
[133]
Marks, P.A. The clinical development of histone deacetylase inhibitors as targeted anticancer drugs. Expert Opin. Investig. Drugs, 2010, 19(9), 1049-1066.
[http://dx.doi.org/10.1517/13543784.2010.510514] [PMID: 20687783]
[134]
Marks, P.A.; Xu, W.S. Histone deacetylase inhibitors: Potential in cancer therapy. J. Cell. Biochem., 2009, 107(4), 600-608.
[http://dx.doi.org/10.1002/jcb.22185] [PMID: 19459166]
[135]
Kelly-Sell, M.J.; Kim, Y.H.; Straus, S.; Benoit, B.; Harrison, C.; Sutherland, K.; Armstrong, R.; Weng, W.K.; Showe, L.C.; Wysocka, M.; Rook, A.H. The histone deacetylase inhibitor, romidepsin, suppresses cellular immune functions of cutaneous T-cell lymphoma patients. Am. J. Hematol., 2012, 87(4), 354-360.
[http://dx.doi.org/10.1002/ajh.23112] [PMID: 22367792]
[136]
Rossi, L.E.; Avila, D.E.; Spallanzani, R.G.; Ziblat, A.; Fuertes, M.B.; Lapyckyj, L.; Croci, D.O.; Rabinovich, G.A.; Domaica, C.I.; Zwirner, N.W. Histone deacetylase inhibitors impair NK cell viability and effector functions through inhibition of activation and receptor expression. J. Leukoc. Biol., 2012, 91(2), 321-331.
[http://dx.doi.org/10.1189/jlb.0711339] [PMID: 22124136]
[137]
Salminen, A.; Tapiola, T.; Korhonen, P.; Suuronen, T. Neuronal apoptosis induced by histone deacetylase inhibitors. Brain Res. Mol. Brain Res., 1998, 61(1-2), 203-206.
[http://dx.doi.org/10.1016/S0169-328X(98)00210-1] [PMID: 9795219]
[138]
Huang, K.L.; Marcora, E.; Pimenova, A.A.; Di Narzo, A.F.; Kapoor, M.; Jin, S.C.; Harari, O.; Bertelsen, S.; Fairfax, B.P.; Czajkowski, J.; Chouraki, V.; Grenier-Boley, B.; Bellenguez, C.; Deming, Y.; McKenzie, A.; Raj, T.; Renton, A.E.; Budde, J.; Smith, A.; Fitzpatrick, A.; Bis, J.C.; DeStefano, A.; Adams, H.H.H.; Ikram, M.A.; van der Lee, S.; Del-Aguila, J.L.; Fernandez, M.V.; Ibañez, L.; Sims, R.; Escott-Price, V.; Mayeux, R.; Haines, J.L.; Farrer, L.A.; Pericak-Vance, M.A.; Lambert, J.C.; van Duijn, C.; Launer, L.; Seshadri, S.; Williams, J.; Amouyel, P.; Schellenberg, G.D.; Zhang, B.; Borecki, I.; Kauwe, J.S.K.; Cruchaga, C.; Hao, K.; Goate, A.M. International Genomics of Alzheimer’s Project; Alzheimer’s Disease Neuroimaging Initiative. A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer’s disease. Nat. Neurosci., 2017, 20(8), 1052-1061.
[http://dx.doi.org/10.1038/nn.4587] [PMID: 28628103]
[139]
Rustenhoven, J.; Smith, A.M.; Smyth, L.C.; Jansson, D.; Scotter, E.L.; Swanson, M.E.V.; Aalderink, M.; Coppieters, N.; Narayan, P.; Handley, R.; Overall, C.; Park, T.I.H.; Schweder, P.; Heppner, P.; Curtis, M.A.; Faull, R.L.M.; Dragunow, M.P.U. 1 regulates Alzheimer’s disease-associated genes in primary human microglia. Mol. Neurodegener., 2018, 13(1), 44.
[http://dx.doi.org/10.1186/s13024-018-0277-1] [PMID: 30124174]
[140]
Jian, W.; Yan, B.; Huang, S.; Qiu, Y. Histone deacetylase 1 activates PU.1 gene transcription through regulating TAF9 deacetylation and transcription factor IID assembly. FASEB J., 2017, 31(9), 4104-4116.
[http://dx.doi.org/10.1096/fj.201700022R] [PMID: 28572446]
[141]
Janczura, K.J.; Volmar, C.H.; Sartor, G.C.; Rao, S.J.; Ricciardi, N.R.; Lambert, G.; Brothers, S.P.; Wahlestedt, C. Inhibition of HDAC3 reverses Alzheimer’s disease-related pathologies in vitro and in the 3xTg-AD mouse model. Proc. Natl. Acad. Sci. USA, 2018, 115(47), E11148-E11157.
[http://dx.doi.org/10.1073/pnas.1805436115] [PMID: 30397132]
[142]
Fang, M.; Wang, J.; Zhang, X.; Geng, Y.; Hu, Z.; Rudd, J.A.; Ling, S.; Chen, W.; Han, S. The miR-124 regulates the expression of BACE1/β-secretase correlated with cell death in Alzheimer’s disease. Toxicol. Lett., 2012, 209(1), 94-105.
[http://dx.doi.org/10.1016/j.toxlet.2011.11.032] [PMID: 22178568]
[143]
Zhu, H.C.; Wang, L.M.; Wang, M.; Song, B.; Tan, S.; Teng, J.F.; Duan, D.X. MicroRNA-195 downregulates Alzheimer’s disease amyloid-β production by targeting BACE1. Brain Res. Bull., 2012, 88(6), 596-601.
[http://dx.doi.org/10.1016/j.brainresbull.2012.05.018] [PMID: 22721728]
[144]
Alvarez-Erviti, L.; Seow, Y.; Yin, H.; Betts, C.; Lakhal, S.; Wood, M.J. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol., 2011, 29(4), 341-345.
[http://dx.doi.org/10.1038/nbt.1807] [PMID: 21423189]
[145]
Junn, E.; Mouradian, M.M. MicroRNAs in neurodegenerative diseases and their therapeutic potential. Pharmacol. Ther., 2012, 133(2), 142-150.
[http://dx.doi.org/10.1016/j.pharmthera.2011.10.002] [PMID: 22008259]
[146]
Rao, J.S.; Rapoport, S.I.; Kim, H.W. Altered neuroinflammatory, arachidonic acid cascade and synaptic markers in postmortem Alzheimer’s disease brain. Transl. Psychiatry, 2017, 7(5), e1127.
[http://dx.doi.org/10.1038/tp.2017.97] [PMID: 28485730]
[147]
Smith, A.R.; Smith, R.G.; Burrage, J.; Troakes, C.; Al-Sarraj, S.; Kalaria, R.N.; Sloan, C.; Robinson, A.C.; Mill, J.; Lunnon, K. A cross-brain regions study of ANK1 DNA methylation in different neurodegenerative diseases. Neurobiol. Aging, 2019, 74, 70-76.
[http://dx.doi.org/10.1016/j.neurobiolaging.2018.09.024] [PMID: 30439595]
[148]
Phipps, A.J.; Vickers, J.C.; Taberlay, P.C.; Woodhouse, A. Neurofilament-labeled pyramidal neurons and astrocytes are deficient in DNA methylation marks in Alzheimer’s disease. Neurobiol. Aging, 2016, 45, 30-42.
[http://dx.doi.org/10.1016/j.neurobiolaging.2016.05.003] [PMID: 27459923]
[149]
Walton, E.; Hass, J.; Liu, J.; Roffman, J.L.; Bernardoni, F.; Roessner, V.; Kirsch, M.; Schackert, G.; Calhoun, V.; Ehrlich, S. Correspondence of DNA methylation between blood and brain tissue and its application to schizophrenia research. Schizophr. Bull., 2016, 42(2), 406-414.
[http://dx.doi.org/10.1093/schbul/sbv074] [PMID: 26056378]
[150]
Cacabelos, R.; Torrellas, C.; Carrera, I.; Cacabelos, P.; Corzo, L.; Fernández-Novoa, L.; Tellado, I.; Carril, J.C.; Aliev, G. Novel therapeutic strategies for dementia. CNS Neurol. Disord. Drug Targets, 2016, 15(2), 141-241.
[http://dx.doi.org/10.2174/1871527315666160202121548] [PMID: 26831267]

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