Apolipoprotein E Gene Revisited: Contribution of Rare Variants to Alzheimer’s Disease Susceptibility in Southern Chinese

Author(s): Anita Yee, Nancy B.Y. Tsui, Rick Y.C. Kwan, Angela Y.M. Leung, Claudia K.Y. Lai, Teresa Chung, Johnson Y.N. Lau, Manson Fok, David L.K. Dai*, Lok-Ting Lau*

Journal Name: Current Alzheimer Research

Volume 18 , Issue 1 , 2021

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Background: APOE ε4 is the best-known risk factor for late-onset alzheimer’s disease (AD). Population studies have demonstrated a relatively low prevalence of APOE ε4 among Chinese population, implying additional risk factors that are Chinese-specific may exist. Apart from - alleles, genetic variation profile along the full-length APOE has rarely been investigated.

Objective: In this study, we filled this gap by comprehensively determining all genetic variations in APOE and investigated their potential associations with late-onset AD and mild cognitive impairment (MCI) in southern Chinese.

Methods: Two hundred and fifty-seven southern Chinese participants were recruited, of whom 69 were AD patients, 83 had MCI, and 105 were normal controls. Full-length APOE from promoter to 3′UTR regions were sequenced. Genetic variants were identified and compared among the three groups.

Results: While APOE ε4 was more significantly found in AD patients, the prevalence of APOE ε4 in southern Chinese AD patients was the lowest when compared to other areas of China and nearby regions, as well as other countries worldwide. We further identified 13 rare non-singleton variants in APOE. Significantly more AD patients carried any of the rare non-singleton variants than MCI and normal subjects. Such difference was observed in the non-carriers of ε4-allele only. Among the identified rare variants, the potential functional impact was predicted for rs532314089, rs553874843, rs533904656 and rs370594287.

Conclusion: Our study suggests an ethnic difference in genetic risk composition of AD in southern Chinese. Rare variants on APOE are a potential candidate for AD risk stratification biomarker in addition to APOE-ε4.

Keywords: Alzheimer's disease, mild cognitive impairment, Chinese, APOE, rare variants, genetics.

Stephan BC, Kurth T, Matthews FE, Brayne C, Dufouil C. Dementia risk prediction in the population: are screening models accurate? Nat Rev Neurol 2010; 6(6): 318-26.
[http://dx.doi.org/10.1038/nrneurol.2010.54] [PMID: 20498679]
Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7(3): 270-9.
[http://dx.doi.org/10.1016/j.jalz.2011.03.008] [PMID: 21514249]
Friedman NP, Miyake A, Young SE, DeFries JC, Corley RP, Hewitt JK. Individual differences in executive functions are almost entirely genetic in origin. J Exp Psychol Gen 2008; 137(2): 201-25.
[http://dx.doi.org/10.1037/0096-3445.137.2.201] [PMID: 18473654]
Gatz M, Reynolds CA, Fratiglioni L, et al. Role of genes and environments for explaining Alzheimer disease. Arch Gen Psychiatry 2006; 63(2): 168-74.
[http://dx.doi.org/10.1001/archpsyc.63.2.168] [PMID: 16461860]
Bertram L, McQueen MB, Mullin K, Blacker D, Tanzi RE. Systematic meta-analyses of Alzheimer disease genetic association studies: The AlzGene database. Nat Genet 2007; 39(1): 17-23.
[http://dx.doi.org/10.1038/ng1934] [PMID: 17192785]
Cosentino S, Scarmeas N, Helzner E, et al. APOE epsilon 4 allele predicts faster cognitive decline in mild Alzheimer disease. Neurology 2008; 70(19 Pt 2): 1842-9.
[http://dx.doi.org/10.1212/01.wnl.0000304038.37421.cc] [PMID: 18401023]
Elias-Sonnenschein LS, Viechtbauer W, Ramakers IH, Verhey FR, Visser PJ. Predictive value of APOE-ε4 allele for progression from MCI to AD-type dementia: A meta-analysis. J Neurol Neurosurg Psychiatry 2011; 82(10): 1149-56.
[http://dx.doi.org/10.1136/jnnp.2010.231555] [PMID: 21493755]
Liu CC, Liu CC, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: Risk, mechanisms and therapy. Nat Rev Neurol 2013; 9(2): 106-18.
[http://dx.doi.org/10.1038/nrneurol.2012.263] [PMID: 23296339]
Pievani M, Galluzzi S, Thompson PM, Rasser PE, Bonetti M, Frisoni GB. APOE4 is associated with greater atrophy of the hippocampal formation in Alzheimer’s disease. Neuroimage 2011; 55(3): 909-19.
[http://dx.doi.org/10.1016/j.neuroimage.2010.12.081] [PMID: 21224004]
Drzezga A, Grimmer T, Henriksen G, et al. Effect of APOE genotype on amyloid plaque load and gray matter volume in Alzheimer disease. Neurology 2009; 72(17): 1487-94.
[http://dx.doi.org/10.1212/WNL.0b013e3181a2e8d0] [PMID: 19339712]
O’Dwyer L, Lamberton F, Matura S, et al. Reduced hippocampal volume in healthy young ApoE4 carriers: An MRI study. PLoS One 2012; 7(11): e48895.
[http://dx.doi.org/10.1371/journal.pone.0048895] [PMID: 23152815]
Sheline YI, Morris JC, Snyder AZ, et al. APOE4 allele disrupts resting state fMRI connectivity in the absence of amyloid plaques or decreased CSF Aβ42. J Neurosci 2010; 30(50): 17035-40.
[http://dx.doi.org/10.1523/JNEUROSCI.3987-10.2010] [PMID: 21159973]
Lambert JC, Araria-Goumidi L, Myllykangas L, et al. Contribution of APOE promoter polymorphisms to Alzheimer’s disease risk. Neurology 2002; 59(1): 59-66.
[http://dx.doi.org/10.1212/WNL.59.1.59] [PMID: 12105308]
Maloney B, Ge YW, Petersen RC, et al. Functional characterization of three single-nucleotide polymorphisms present in the human APOE promoter sequence: Differential effects in neuronal cells and on DNA-protein interactions. Am J Med Genet B Neuropsychiatr Genet 2010; 153B(1): 185-201.
[PMID: 19504470]
Du Y, Chen X, Wei X, et al. NF-(kappa)B mediates amyloid beta peptide-stimulated activity of the human apolipoprotein E gene promoter in human astroglial cells. Brain Res Mol Brain Res 2005; 136(1-2): 177-88.
[http://dx.doi.org/10.1016/j.molbrainres.2005.02.001] [PMID: 15893602]
Dorszewska J, Prendecki M, Oczkowska A, Dezor M, Kozubski W. Molecular basis of familial and sporadic Alzheimer’s disease. Curr Alzheimer Res 2016; 13(9): 952-63.
[http://dx.doi.org/10.2174/1567205013666160314150501] [PMID: 26971934]
Lambert JC, Heath S, Even G, et al. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Nat Genet 2009; 41(10): 1094-9.
[http://dx.doi.org/10.1038/ng.439] [PMID: 19734903]
Harold D, Abraham R, Hollingworth P, et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat Genet 2009; 41(10): 1088-93.
[http://dx.doi.org/10.1038/ng.440] [PMID: 19734902]
Hollingworth P, Harold D, Sims R, et al. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease. Nat Genet 2011; 43(5): 429-35.
[http://dx.doi.org/10.1038/ng.803] [PMID: 21460840]
Naj AC, Jun G, Beecham GW, et al. Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer’s disease. Nat Genet 2011; 43(5): 436-41.
[http://dx.doi.org/10.1038/ng.801] [PMID: 21460841]
Seshadri S, Fitzpatrick AL, Ikram MA, et al. Genome-wide analysis of genetic loci associated with Alzheimer disease. JAMA 2010; 303(18): 1832-40.
[http://dx.doi.org/10.1001/jama.2010.574] [PMID: 20460622]
Lambert JC, Ibrahim-Verbaas CA, Harold D, et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat Genet 2013; 45(12): 1452-8.
[http://dx.doi.org/10.1038/ng.2802] [PMID: 24162737]
Jonsson T, Stefansson H, Steinberg S, et al. Variant of TREM2 associated with the risk of Alzheimer’s disease. N Engl J Med 2013; 368(2): 107-16.
[http://dx.doi.org/10.1056/NEJMoa1211103] [PMID: 23150908]
Jin C, Li W, Yuan J, Xu W, Cheng Z. Association of the CR1 polymorphism with late-onset Alzheimer’s disease in Chinese Han populations: A meta-analysis. Neurosci Lett 2012; 527(1): 46-9.
[http://dx.doi.org/10.1016/j.neulet.2012.08.032] [PMID: 22960360]
Li X, Shen N, Zhang S, et al. CD33 rs3865444 polymorphism contributes to Alzheimer’s disease susceptibility in Chinese, European, and North American populations. Mol Neurobiol 2015; 52(1): 414-21.
[http://dx.doi.org/10.1007/s12035-014-8880-9] [PMID: 25186233]
Yee A, Tsui NB, Chang YN, et al. Alzheimer’s disease: Insights for risk evaluation and prevention in the Chinese population and the need for a comprehensive programme in Hong Kong/China. Hong Kong Med J 2018; 24(5): 492-500.
[http://dx.doi.org/10.12809/hkmj187244] [PMID: 30232267]
Liu M, Bian C, Zhang J, Wen F. Apolipoprotein E gene polymorphism and Alzheimer’s disease in Chinese population: a meta-analysis. Sci Rep 2014; 4: 4383.
[http://dx.doi.org/10.1038/srep04383] [PMID: 24632849]
Ward A, Crean S, Mercaldi CJ, et al. Prevalence of apolipoprotein E4 genotype and homozygotes (APOE e4/4) among patients diagnosed with Alzheimer’s disease: A systematic review and meta-analysis. Neuroepidemiology 2012; 38(1): 1-17.
[http://dx.doi.org/10.1159/000334607] [PMID: 22179327]
Zhou X, Chen Y, Mok KY, et al. Identification of genetic risk factors in the Chinese population implicates a role of immune system in Alzheimer’s disease pathogenesis. Proc Natl Acad Sci USA 2018; 115(8): 1697-706.
[http://dx.doi.org/10.1073/pnas.1715554115] [PMID: 29432188]
Tsui NBY, Cheng G, Chung T, et al. Population-wide genetic risk prediction of complex diseases: A pilot feasibility study in Macau population for precision public healthcare planning. Sci Rep 2018; 8(1): 1853.
[http://dx.doi.org/10.1038/s41598-017-19017-y] [PMID: 29382849]
McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7(3): 263-9.
[http://dx.doi.org/10.1016/j.jalz.2011.03.005] [PMID: 21514250]
Weckx S, Del-Favero J, Rademakers R, et al. novoSNP, a novel computational tool for sequence variation discovery. Genome Res 2005; 15(3): 436-42.
[http://dx.doi.org/10.1101/gr.2754005] [PMID: 15741513]
Mathelier A, Fornes O, Arenillas DJ, et al. JASPAR 2016: A major expansion and update of the open-access database of transcription factor binding profiles. Nucleic Acids Res 2016; 44(D1): D110-5.
[http://dx.doi.org/10.1093/nar/gkv1176] [PMID: 26531826]
Consortium GT. The Genotype-Tissue Expression (GTEx) project. Nat Genet 2013; 45(6): 580-5.
[http://dx.doi.org/10.1038/ng.2653] [PMID: 23715323]
Su AI, Wiltshire T, Batalov S, et al. A gene atlas of the mouse and human protein-encoding transcriptomes. Proc Natl Acad Sci USA 2004; 101(16): 6062-7.
[http://dx.doi.org/10.1073/pnas.0400782101] [PMID: 15075390]
Uhlén M, Fagerberg L, Hallström BM, et al. Proteomics. Tissue-based map of the human proteome. Science 2015; 347(6220): 1260419.
[http://dx.doi.org/10.1126/science.1260419] [PMID: 25613900]
Almagro Armenteros JJ, Tsirigos KD, Sønderby CK, et al. SignalP 5.0 improves signal peptide predictions using deep neural networks. Nat Biotechnol 2019; 37(4): 420-3.
[http://dx.doi.org/10.1038/s41587-019-0036-z] [PMID: 30778233]
Chen J, Li Q, Wang J. Topology of human apolipoprotein E3 uniquely regulates its diverse biological functions. Proc Natl Acad Sci USA 2011; 108(36): 14813-8.
[http://dx.doi.org/10.1073/pnas.1106420108] [PMID: 21873229]
Pandurangan AP, Ochoa-Montaño B, Ascher DB, Blundell TL. SDM: a server for predicting effects of mutations on protein stability. Nucleic Acids Res 2017; 45(W1): W229-35.
[http://dx.doi.org/10.1093/nar/gkx439] [PMID: 28525590]
Vejnar CE, Zdobnov EM. MiRmap: Comprehensive prediction of microRNA target repression strength. Nucleic Acids Res 2012; 40(22): 11673-83.
[http://dx.doi.org/10.1093/nar/gks901] [PMID: 23034802]
Somel M, Guo S, Fu N, et al. MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain. Genome Res 2010; 20(9): 1207-18.
[http://dx.doi.org/10.1101/gr.106849.110] [PMID: 20647238]
Sharpe D. Your chi-square test is statistically significant: Now what? Pract Assess, Res Eval 2015; 20(8)
Mak YT, Chiu H, Woo J, et al. Apolipoprotein E genotype and Alzheimer’s disease in Hong Kong elderly Chinese. Neurology 1996; 46(1): 146-9.
[http://dx.doi.org/10.1212/WNL.46.1.146] [PMID: 8559364]
Hong CJ, Liu TY, Liu HC, et al. Epsilon 4 allele of apolipoprotein E increases risk of Alzheimer’s disease in a Chinese population. Neurology 1996; 46(6): 1749-51.
[http://dx.doi.org/10.1212/WNL.46.6.1749] [PMID: 8649585]
Katzman R, Zhang MY, Chen PJ, et al. Effects of apolipoprotein E on dementia and aging in the Shanghai Survey of dementia. Neurology 1997; 49(3): 779-85.
[http://dx.doi.org/10.1212/WNL.49.3.779] [PMID: 9305340]
Hu CJ, Sung SM, Liu HC, Chang JG. Association of apolipoprotein E genotype and intronic polymorphism of the presenilin-1 gene with Alzheimer’s disease in elderly Taiwan Chinese. J Neurol Sci 1998; 157(2): 158-61.
[http://dx.doi.org/10.1016/S0022-510X(98)00052-5] [PMID: 9619639]
Hu CJ, Sung SM, Liu HC, et al. Genetic risk factors of sporadic Alzheimer’s disease among Chinese in Taiwan. J Neurol Sci 2000; 181(1-2): 127-31.
[http://dx.doi.org/10.1016/S0022-510X(00)00443-3] [PMID: 11099722]
Zhang JG, Yang JG, Lin ZX, et al. Apolipoprotein E epsilon4 allele is a risk factor for late-onset Alzheimer’s disease and vascular dementia in Han Chinese. Int J Geriatr Psychiatry 2001; 16(4): 438-9.
[http://dx.doi.org/10.1002/gps.330] [PMID: 11333435]
Lai CL, Tai CT, Lin SR, Lin RT, Yang YH, Liu CK. Apolipoprotein E in Taiwan Chinese patients with dementia. Dement Geriatr Cogn Disord 2003; 16(4): 208-11.
[http://dx.doi.org/10.1159/000072804] [PMID: 14512715]
Zhou X, Miao H, Rausch WD, et al. Association between apolipoprotein E gene polymorphism and Alzheimer’s disease in Uighur and Han populations. Psychogeriatrics 2012; 12(2): 83-7.
[http://dx.doi.org/10.1111/j.1479-8301.2011.00389.x] [PMID: 22712640]
Ji Y, Liu M, Huo YR, et al. Apolipoprotein Ε ε4 frequency is increased among Chinese patients with frontotemporal dementia and Alzheimer’s disease. Dement Geriatr Cogn Disord 2013; 36(3-4): 163-70.
[http://dx.doi.org/10.1159/000350872] [PMID: 23887281]
Wang X, Wang H, Li H, Li T, Yu X. Frequency of the apolipoprotein E ε4 allele in a memory clinic cohort in Beijing: A naturalistic descriptive study. PLoS One 2014; 9(6): e99130.
[http://dx.doi.org/10.1371/journal.pone.0099130] [PMID: 24914687]
Wu P, Li HL, Liu ZJ, et al. Associations between apolipoprotein E gene polymorphisms and Alzheimer’s disease risk in a large Chinese Han population. Clin Interv Aging 2015; 10: 371-8.
[PMID: 25673977]
Chen KL, Sun YM, Zhou Y, Zhao QH, Ding D, Guo QH. Associations between APOE polymorphisms and seven diseases with cognitive impairment including Alzheimer’s disease, frontotemporal dementia, and dementia with Lewy bodies in southeast China. Psychiatr Genet 2016; 26(3): 124-31.
[http://dx.doi.org/10.1097/YPG.0000000000000126] [PMID: 26981880]
Neu SC, Pa J, Kukull W, et al. Apolipoprotein E genotype and sex risk factors for Alzheimer disease: A meta-analysis. JAMA Neurol 2017; 74(10): 1178-89.
[http://dx.doi.org/10.1001/jamaneurol.2017.2188] [PMID: 28846757]
Corrada MM, Paganini-Hill A, Berlau DJ, Kawas CH. Apolipoprotein E genotype, dementia, and mortality in the oldest old: The 90+ study. Alzheimers Dement 2013; 9(1): 12-8.
[http://dx.doi.org/10.1016/j.jalz.2011.12.004] [PMID: 23123227]
Pericak-Vance MA, Bebout JL, Gaskell PC Jr, et al. Linkage studies in familial Alzheimer disease: Evidence for chromosome 19 linkage. Am J Hum Genet 1991; 48(6): 1034-50.
[PMID: 2035524]
Strittmatter WJ, Saunders AM, Schmechel D, et al. Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci USA 1993; 90(5): 1977-81.
[http://dx.doi.org/10.1073/pnas.90.5.1977] [PMID: 8446617]
Farrer LA, Cupples LA, Haines JL, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. JAMA 1997; 278(16): 1349-56.
[http://dx.doi.org/10.1001/jama.1997.03550160069041] [PMID: 9343467]
Riedel BC, Thompson PM, Brinton RD. Age, APOE and sex: Triad of risk of Alzheimer’s disease. J Steroid Biochem Mol Biol 2016; 160: 134-47.
[http://dx.doi.org/10.1016/j.jsbmb.2016.03.012] [PMID: 26969397]
Juva K, Verkkoniemi A, Viramo P, et al. APOE epsilon4 does not predict mortality, cognitive decline, or dementia in the oldest old. Neurology 2000; 54(2): 412-5.
[http://dx.doi.org/10.1212/WNL.54.2.412] [PMID: 10668704]
Brookmeyer R, Corrada MM, Curriero FC, Kawas C. Survival following a diagnosis of Alzheimer disease. Arch Neurol 2002; 59(11): 1764-7.
[http://dx.doi.org/10.1001/archneur.59.11.1764] [PMID: 12433264]
Schächter F, Faure-Delanef L, Guénot F, et al. Genetic associations with human longevity at the APOE and ACE loci. Nat Genet 1994; 6(1): 29-32.
[http://dx.doi.org/10.1038/ng0194-29] [PMID: 8136829]
Drenos F, Kirkwood TB. Selection on alleles affecting human longevity and late-life disease: The example of apolipoprotein E. PLoS One 2010; 5(4): e10022.
[http://dx.doi.org/10.1371/journal.pone.0010022] [PMID: 20368805]
Oveisgharan S, Buchman AS, Yu L, et al. APOE ε2ε4 genotype, incident AD and MCI, cognitive decline, and AD pathology in older adults. Neurology 2018; 90(24): e2127-34.
[http://dx.doi.org/10.1212/WNL.0000000000005677] [PMID: 29752306]
Ohm TG, Scharnagl H, März W, Bohl J. Apolipoprotein E isoforms and the development of low and high Braak stages of Alzheimer’s disease-related lesions. Acta Neuropathol 1999; 98(3): 273-80.
[http://dx.doi.org/10.1007/s004010051080] [PMID: 10483785]
Berlau DJ, Corrada MM, Head E, Kawas CH. APOE epsilon2 is associated with intact cognition but increased Alzheimer pathology in the oldest old. Neurology 2009; 72(9): 829-34.
[http://dx.doi.org/10.1212/01.wnl.0000343853.00346.a4] [PMID: 19255410]
O’Donoghue MC, Murphy SE, Zamboni G, Nobre AC, Mackay CE. APOE genotype and cognition in healthy individuals at risk of Alzheimer’s disease: A review. Cortex 2018; 104: 103-23.
[http://dx.doi.org/10.1016/j.cortex.2018.03.025] [PMID: 29800787]
Lindenberger U, Nagel IE, Chicherio C, Li SC, Heekeren HR, Bäckman L. Age-related decline in brain resources modulates genetic effects on cognitive functioning. Front Neurosci 2008; 2(2): 234-44.
[http://dx.doi.org/10.3389/neuro.01.039.2008] [PMID: 19225597]
Bomba L, Walter K, Soranzo N. The impact of rare and low-frequency genetic variants in common disease. Genome Biol 2017; 18(1): 77.
[http://dx.doi.org/10.1186/s13059-017-1212-4] [PMID: 28449691]
Lord J, Lu AJ, Cruchaga C. Identification of rare variants in Alzheimer’s disease. Front Genet 2014; 5: 369.
[http://dx.doi.org/10.3389/fgene.2014.00369] [PMID: 25389433]
Medway CW, Abdul-Hay S, Mims T, et al. ApoE variant p.V236E is associated with markedly reduced risk of Alzheimer’s disease. Mol Neurodegener 2014; 9: 11.
[http://dx.doi.org/10.1186/1750-1326-9-11] [PMID: 24607147]
de Geus E, Goldberg T, Boomsma DI, Posthuma D. Imaging the genetics of brain structure and function. Biol Psychol 2008; 79(1): 1-8.
[http://dx.doi.org/10.1016/j.biopsycho.2008.04.002] [PMID: 18487006]
Veyrac A, Besnard A, Caboche J, Davis S, Laroche S. The transcription factor Zif268/Egr1, brain plasticity, and memory. Prog Mol Biol Transl Sci 2014; 122: 89-129.
[http://dx.doi.org/10.1016/B978-0-12-420170-5.00004-0] [PMID: 24484699]
Qin X, Wang Y, Paudel HK. Early growth response 1 (Egr-1) is a transcriptional activator of β-Secretase 1 (BACE-1) in the brain. J Biol Chem 2016; 291(42): 22276-87.
[http://dx.doi.org/10.1074/jbc.M116.738849] [PMID: 27576688]
O’Brien RJ, Wong PC. Amyloid precursor protein processing and Alzheimer’s disease. Annu Rev Neurosci 2011; 34: 185-204.
[http://dx.doi.org/10.1146/annurev-neuro-061010-113613] [PMID: 21456963]
Butovsky O, Jedrychowski MP, Moore CS, et al. Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Nat Neurosci 2014; 17(1): 131-43.
[http://dx.doi.org/10.1038/nn.3599] [PMID: 24316888]
Krasemann S, Madore C, Cialic R, Baufeld C, Calcagno N, El Fatimy R. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 2017; 47(3): 566-81.
Wang WX, Huang Q, Hu Y, Stromberg AJ, Nelson PT. Patterns of microRNA expression in normal and early Alzheimer’s disease human temporal cortex: White matter versus gray matter. Acta Neuropathol 2011; 121(2): 193-205.
[http://dx.doi.org/10.1007/s00401-010-0756-0] [PMID: 20936480]
Liu C, Teng ZQ, Santistevan NJ, et al. Epigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation. Cell Stem Cell 2010; 6(5): 433-44.
[http://dx.doi.org/10.1016/j.stem.2010.02.017] [PMID: 20452318]
Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin 2016; 66(2): 115-32.
[http://dx.doi.org/10.3322/caac.21338] [PMID: 26808342]

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Year: 2021
Published on: 24 March, 2021
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DOI: 10.2174/1567205018666210324111401
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