Abstract
Background: Approximately 40 independent Single Nucleotide Polymorphisms (SNPs) have been associated with Alzheimer’s Disease (AD) or cognitive decline in genome-wide association studies.
Objective: We aimed to evaluate the joint effect of genetic polymorphisms and environmental factors on the progression from Mild Cognitive Impairment (MCI) to AD (MCI-AD progression) in a Chinese community cohort. Methods: Demographic, DNA and incident AD diagnosis data were derived from the follow-up of 316 participants with MCI at baseline of the Shanghai Aging Study. The associations of 40 SNPs and environmental predictors with MCI-AD progression were assessed using the Kaplan-Meier method with the log-rank test and Cox regression model. Results: Rs4147929 at ATP-binding cassette family A member 7 (ABCA7) (AG/AA vs. GG, hazard ratio [HR] = 2.43, 95% confidence interval [CI] 1.24-4.76) and body mass index (BMI) (overweight vs. non-overweight, HR = 0.41, 95% CI 0.22-0.78) were independent predictors of MCI-AD progression. In the combined analyses, MCI participants with the copresence of non-overweight BMI and the ABCA7 rs4147929 (AG/AA) risk genotype had an approximately 6-fold higher risk of MCI-AD progression than those with an overweight BMI and a non-risk genotype (HR = 6.77, 95% CI 2.60-17.63). However, a nonsignificant result was found when participants carried only one of these two risk factors (nonoverweight BMI and AG/AA of ABCA7 rs4147929). Conclusion: ABCA7 rs4147929 and BMI jointly affect MCI-AD progression. MCI participants with the rs4147929 risk genotype may benefit from maintaining an overweight BMI level with regard to their risk for incident AD.Keywords: Mild cognitive impairment, progression, Alzheimer’s disease, ABCA7, body mass index, risk factor.
[2]
Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med 362(4): 329-44. (2010).
[http://dx.doi.org/10.1056/NEJMra0909142] [PMID: 20107219]
[http://dx.doi.org/10.1056/NEJMra0909142] [PMID: 20107219]
[3]
Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, DeKosky ST. Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 56(9): 1133-42. (2001).
[http://dx.doi.org/10.1212/WNL.56.9.1133] [PMID: 11342677]
[http://dx.doi.org/10.1212/WNL.56.9.1133] [PMID: 11342677]
[4]
Winblad B, Palmer K, Kivipelto M, et al. Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 256(3): 240-6. (2004).
[http://dx.doi.org/10.1111/j.1365-2796.2004.01380.x] [PMID: 15324367]
[http://dx.doi.org/10.1111/j.1365-2796.2004.01380.x] [PMID: 15324367]
[5]
Bruscoli M, Lovestone S. Is MCI really just early dementia? A systematic review of conversion studies. Int Psychogeriatr 16(2): 129-40. (2004).
[http://dx.doi.org/10.1017/S1041610204000092] [PMID: 15318760]
[http://dx.doi.org/10.1017/S1041610204000092] [PMID: 15318760]
[6]
Mitchell AJ, Shiri-Feshki M. Rate of progression of mild cognitive impairment to dementia--meta-analysis of 41 robust inception cohort studies. Acta Psychiatr Scand 119(4): 252-65. (2009).
[http://dx.doi.org/10.1111/j.1600-0447.2008.01326.x] [PMID: 19236314]
[http://dx.doi.org/10.1111/j.1600-0447.2008.01326.x] [PMID: 19236314]
[7]
Petersen RC, Aisen PS, Beckett LA, et al. Alzheimer’s Disease Neuroimaging Initiative (ADNI): clinical characterization. Neurology 74(3): 201-9. (2010).
[http://dx.doi.org/10.1212/WNL.0b013e3181cb3e25] [PMID: 20042704]
[http://dx.doi.org/10.1212/WNL.0b013e3181cb3e25] [PMID: 20042704]
[8]
Ding D, Zhao Q, Guo Q, et al. Progression and predictors of mild cognitive impairment in Chinese elderly: A prospective follow-up in the Shanghai Aging Study. Alzheimers Dement (Amst) 4: 28-36. (2016).
[http://dx.doi.org/10.1016/j.dadm.2016.03.004] [PMID: 27489876]
[http://dx.doi.org/10.1016/j.dadm.2016.03.004] [PMID: 27489876]
[9]
Montero-Odasso MM, Sarquis-Adamson Y, Speechley M, et al. Association of dual-task gait with incident dementia in mild cognitive impairment: results from the gait and brain study. JAMA Neurol 74(7): 857-65. (2017).
[http://dx.doi.org/10.1001/jamaneurol.2017.0643] [PMID: 28505243]
[http://dx.doi.org/10.1001/jamaneurol.2017.0643] [PMID: 28505243]
[10]
Xu WL, Caracciolo B, Wang HX, Santoni G, Winblad B, Fratiglioni L. Accelerated progression from mild cognitive impairment to dementia among APOE ε4ε4 carriers. J Alzheimers Dis 33(2): 507-15. (2013).
[http://dx.doi.org/10.3233/JAD-2012-121369] [PMID: 23247007]
[http://dx.doi.org/10.3233/JAD-2012-121369] [PMID: 23247007]
[11]
Zhou B, Zhao Q, Kojima S, et al. One-year outcome of shanghai mild cognitive impairment cohort study. Curr Alzheimer Res 16(2): 156-65. (2019).
[http://dx.doi.org/10.2174/1567205016666181128151144] [PMID: 30484408]
[http://dx.doi.org/10.2174/1567205016666181128151144] [PMID: 30484408]
[12]
Zhou R, Zhou H, Rui L, Xu J. Bone loss and osteoporosis are associated with conversion from mild cognitive impairment to Alzheimer’s disease. Curr Alzheimer Res 11(7): 706-13. (2014).
[http://dx.doi.org/10.2174/1567205011666140812115818] [PMID: 25115539]
[http://dx.doi.org/10.2174/1567205011666140812115818] [PMID: 25115539]
[13]
Chartier-Harlin MC, Parfitt M, Legrain S, et al. Apolipoprotein E, epsilon 4 allele as a major risk factor for sporadic early and late-onset forms of Alzheimer’s disease: analysis of the 19q13.2 chromosomal region. Hum Mol Genet 3(4): 569-74. (1994).
[http://dx.doi.org/10.1093/hmg/3.4.569] [PMID: 8069300]
[http://dx.doi.org/10.1093/hmg/3.4.569] [PMID: 8069300]
[14]
Corder EH, Saunders AM, Strittmatter WJ, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261(5123): 921-3. (1993).
[http://dx.doi.org/10.1126/science.8346443] [PMID: 8346443]
[http://dx.doi.org/10.1126/science.8346443] [PMID: 8346443]
[15]
Ashford JW, Mortimer JA. Non-familial Alzheimer’s disease is mainly due to genetic factors. J Alzheimers Dis 4(3): 169-77. (2002).
[http://dx.doi.org/10.3233/JAD-2002-4307] [PMID: 12226536]
[http://dx.doi.org/10.3233/JAD-2002-4307] [PMID: 12226536]
[16]
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 41(10): 1088-93. (2009).
[http://dx.doi.org/10.1038/ng.440] [PMID: 19734902]
[http://dx.doi.org/10.1038/ng.440] [PMID: 19734902]
[17]
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 43(5): 429-35. (2011).
[http://dx.doi.org/10.1038/ng.803] [PMID: 21460840]
[http://dx.doi.org/10.1038/ng.803] [PMID: 21460840]
[18]
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 45(12): 1452-8. (2013).
[http://dx.doi.org/10.1038/ng.2802] [PMID: 24162737]
[http://dx.doi.org/10.1038/ng.2802] [PMID: 24162737]
[19]
Naj AC, Beecham GW, Martin ER, et al. Dementia revealed: novel chromosome 6 locus for late-onset Alzheimer disease provides genetic evidence for folate-pathway abnormalities. PLoS Genet 6(9): e1001130 (2010).
[http://dx.doi.org/10.1371/journal.pgen.1001130] [PMID: 20885792]
[http://dx.doi.org/10.1371/journal.pgen.1001130] [PMID: 20885792]
[20]
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 43(5): 436-41. (2011).
[http://dx.doi.org/10.1038/ng.801] [PMID: 21460841]
[http://dx.doi.org/10.1038/ng.801] [PMID: 21460841]
[21]
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]
[http://dx.doi.org/10.1001/jama.2010.574] [PMID: 20460622]
[22]
De Jager PL, Shulman JM, Chibnik LB, et al. A genome-wide scan for common variants affecting the rate of age-related cognitive decline. Neurobiol Aging 33(5): 1017.e1-1017.e15. (2012).
[http://dx.doi.org/10.1016/j.neurobiolaging.2011.09.033] [PMID: 22054870]
[http://dx.doi.org/10.1016/j.neurobiolaging.2011.09.033] [PMID: 22054870]
[23]
Hu X, Pickering EH, Hall SK, Naik S, Liu YC, Soares H, et al. Genome-wide association study identifies multiple novel loci associated with disease progression in subjects with mild cognitive impairment. ransl Psychiatry 1(11): 1e54. (2011).
[http://dx.doi.org/10.1038/tp.2011.50] [PMID: 22833209]
[http://dx.doi.org/10.1038/tp.2011.50] [PMID: 22833209]
[24]
Li QS, Parrado AR, Samtani MN, Narayan VA. Variations in the FRA10AC1 fragile site and 15q21 are associated with cerebrospinal fluid Aβ1-42 level. PLoS One 10(8): e0134000 (2015).
[http://dx.doi.org/10.1371/journal.pone.0134000] [PMID: 26252872]
[http://dx.doi.org/10.1371/journal.pone.0134000] [PMID: 26252872]
[25]
Sherva R, Tripodis Y, Bennett DA, et al. Genome-wide association study of the rate of cognitive decline in Alzheimer’s disease. Alzheimers Dement 10(1): 45-52. (2014).
[http://dx.doi.org/10.1016/j.jalz.2013.01.008] [PMID: 23535033]
[http://dx.doi.org/10.1016/j.jalz.2013.01.008] [PMID: 23535033]
[26]
Zhang C, Pierce BL. Genetic susceptibility to accelerated cognitive decline in the US Health and Retirement Study. Neurobiol Aging 2014; 35(6): 1512.e11.
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.12.021] [PMID: 24468470]
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.12.021] [PMID: 24468470]
[27]
Xiao Q, Liu ZJ, Tao S, et al. Risk prediction for sporadic Alzheimer’s disease using genetic risk score in the Han Chinese population. Oncotarget 6(35): 36955-64. (2015).
[http://dx.doi.org/10.18632/oncotarget.6271] [PMID: 26543236]
[http://dx.doi.org/10.18632/oncotarget.6271] [PMID: 26543236]
[28]
Jiang S, Zhang CY, Tang L, Zhao LX, Chen HZ, Qiu Y. Integrated genomic analysis revealed associated genes for Alzheimer’s disease in APOE4 non-carriers. Curr Alzheimer Res 16(8): 753-63. (2019).
[http://dx.doi.org/10.2174/1567205016666190823124724] [PMID: 31441725]
[http://dx.doi.org/10.2174/1567205016666190823124724] [PMID: 31441725]
[29]
Reitz C, Jun G, Naj A, et al. Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ϵ4,and the risk of late-onset Alzheimer disease in African Americans. JAMA 309(14): 1483-92. (2013).
[http://dx.doi.org/10.1001/jama.2013.2973] [PMID: 23571587]
[http://dx.doi.org/10.1001/jama.2013.2973] [PMID: 23571587]
[30]
Aikawa T, Holm ML, Kanekiyo T. ABCA7 and pathogenic pathways of Alzheimer’s disease. Brain Sci 8(2): 27. (2018).
[http://dx.doi.org/10.3390/brainsci8020027] [PMID: 29401741]
[http://dx.doi.org/10.3390/brainsci8020027] [PMID: 29401741]
[31]
Dorszewska J, Prendecki M, Oczkowska A, Dezor M, Kozubski W. Molecular basis of familial and sporadic Alzheimer’s disease. Curr Alzheimer Res 13(9): 952-63. (2016).
[http://dx.doi.org/10.2174/1567205013666160314150501] [PMID: 26971934]
[http://dx.doi.org/10.2174/1567205013666160314150501] [PMID: 26971934]
[32]
Kivipelto M, Rovio S, Ngandu T, et al. Apolipoprotein E epsilon4 magnifies lifestyle risks for dementia: a population-based study. J Cell Mol Med 12(6B): 2762-71. (2008).
[http://dx.doi.org/10.1111/j.1582-4934.2008.00296.x] [PMID: 18318693]
[http://dx.doi.org/10.1111/j.1582-4934.2008.00296.x] [PMID: 18318693]
[33]
Luck T, Riedel-Heller SG, Luppa M, et al. Apolipoprotein E epsilon 4 genotype and a physically active lifestyle in late life: analysis of gene-environment interaction for the risk of dementia and Alzheimer’s disease dementia. Psychol Med 44(6): 1319-29. (2014).
[http://dx.doi.org/10.1017/S0033291713001918] [PMID: 23883793]
[http://dx.doi.org/10.1017/S0033291713001918] [PMID: 23883793]
[34]
Rajan KB, Skarupski KA, Rasmussen HE, Evans DA. Gene-environment interaction of body mass index and apolipoprotein E ε4 allele on cognitive decline. Alzheimer Dis Assoc Disord 28(2): 134-40. (2014).
[http://dx.doi.org/10.1097/WAD.0000000000000013] [PMID: 24145695]
[http://dx.doi.org/10.1097/WAD.0000000000000013] [PMID: 24145695]
[35]
Rovio S, Kåreholt I, Helkala EL, et al. Leisure-time physical activity at midlife and the risk of dementia and Alzheimer’s disease. Lancet Neurol 4(11): 705-11. (2005).
[http://dx.doi.org/10.1016/S1474-4422(05)70198-8] [PMID: 16239176]
[http://dx.doi.org/10.1016/S1474-4422(05)70198-8] [PMID: 16239176]
[36]
Maloney B, Sambamurti K, Zawia N, Lahiri DK. Applying epigenetics to Alzheimer’s disease via the latent early-life associated regulation (LEARn) model. Curr Alzheimer Res 9(5): 589-99. (2012).
[http://dx.doi.org/10.2174/156720512800617955] [PMID: 22300406]
[http://dx.doi.org/10.2174/156720512800617955] [PMID: 22300406]
[37]
Maloney B, Lahiri DK. Epigenetics of dementia: understanding the disease as a transformation rather than a state. Lancet Neurol 15(7): 760-74. (2016).
[http://dx.doi.org/10.1016/S1474-4422(16)00065-X] [PMID: 27302240]
[http://dx.doi.org/10.1016/S1474-4422(16)00065-X] [PMID: 27302240]
[38]
Lin E, Tsai SJ, Kuo PH, Liu YL, Yang AC, Kao CF. Association and interaction effects of Alzheimer’s disease-associated genes and lifestyle on cognitive aging in older adults in a Taiwanese population. Oncotarget 8(15): 24077-87. (2017).
[PMID: 28199971]
[PMID: 28199971]
[39]
Zhang H, Zheng W, Hua L, et al. Interaction between PPAR γ and SORL1 gene with Late-Onset Alzheimer’s disease in Chinese Han Population. Oncotarget 8(29): 48313-20. (2017).
[http://dx.doi.org/10.18632/oncotarget.15691] [PMID: 28427149]
[http://dx.doi.org/10.18632/oncotarget.15691] [PMID: 28427149]
[40]
Ding D, Zhao Q, Guo Q, et al. Prevalence of mild cognitive impairment in an urban community in China: a cross-sectional analysis of the Shanghai Aging Study. Alzheimers Dement 11(3): 300-9.e2. (2015).
[http://dx.doi.org/10.1016/j.jalz.2013.11.002] [PMID: 24613707]
[http://dx.doi.org/10.1016/j.jalz.2013.11.002] [PMID: 24613707]
[41]
Lim WS, Chong MS, Sahadevan S. Utility of the clinical dementia rating in Asian populations. Clin Med Res 5(1): 61-70. (2007).
[http://dx.doi.org/10.3121/cmr.2007.693] [PMID: 17456836]
[http://dx.doi.org/10.3121/cmr.2007.693] [PMID: 17456836]
[42]
Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 9(3): 179-86. (1969).
[http://dx.doi.org/10.1093/geront/9.3_Part_1.179] [PMID: 5349366]
[http://dx.doi.org/10.1093/geront/9.3_Part_1.179] [PMID: 5349366]
[44]
Smirnov DA, Morley M, Shin E, Spielman RS, Cheung VG. Genetic analysis of radiation-induced changes in human gene expression. Nature 459(7246): 587-91. (2009).
[http://dx.doi.org/10.1038/nature07940] [PMID: 19349959]
[http://dx.doi.org/10.1038/nature07940] [PMID: 19349959]
[45]
Wang PN, Lirng JF, Lin KN, Chang FC, Liu HC. Prediction of Alzheimer’s disease in mild cognitive impairment: a prospective study in Taiwan. Neurobiol Aging 27(12): 1797-806. (2006).
[http://dx.doi.org/10.1016/j.neurobiolaging.2005.10.002] [PMID: 16321457]
[http://dx.doi.org/10.1016/j.neurobiolaging.2005.10.002] [PMID: 16321457]
[46]
Norton S, Matthews FE, Barnes DE, Yaffe K, Brayne C. Potential for primary prevention of Alzheimer’s disease: an analysis of population-based data. Lancet Neurol 13(8): 788-94. (2014).
[http://dx.doi.org/10.1016/S1474-4422(14)70136-X] [PMID: 25030513]
[http://dx.doi.org/10.1016/S1474-4422(14)70136-X] [PMID: 25030513]
[47]
Klimova B, Maresova P, Kuca K. Alzheimer’s Disease: physical activities as an effective intervention tool - a mini-review. Curr Alzheimer Res 16(2): 166-71. (2019).
[http://dx.doi.org/10.2174/1567205015666181002132021] [PMID: 30277151]
[http://dx.doi.org/10.2174/1567205015666181002132021] [PMID: 30277151]
[48]
Romero-Sevilla R, Casado-Naranjo I, Portilla-Cuenca JC, Duque-de San Juan B, Fuentes JM, Lopez-Espuela F. Vascular risk factors and lesions of vascular nature in magnetic resonance as predictors of progression to dementia in patients with mild cognitive impairment. Curr Alzheimer Res 15(7): 671-8. (2018).
[http://dx.doi.org/10.2174/1567205015666180119100840] [PMID: 29357793]
[http://dx.doi.org/10.2174/1567205015666180119100840] [PMID: 29357793]
[49]
Osone A, Arai R, Hakamada R, Shimoda K. Impact of lifestyle-related disease on conversion and reversion in patients with mild cognitive impairment: after 12 months of follow-up. Int J Geriatr Psychiatry 31(7): 740-8. (2016).
[http://dx.doi.org/10.1002/gps.4386] [PMID: 26593034]
[http://dx.doi.org/10.1002/gps.4386] [PMID: 26593034]
[50]
Cataldo JK, Prochaska JJ, Glantz SA. Cigarette smoking is a risk factor for Alzheimer’s Disease: an analysis controlling for tobacco industry affiliation. J Alzheimers Dis 19(2): 465-80.
[http://dx.doi.org/10.3233/JAD-2010-1240] [PMID: 20110594]
[http://dx.doi.org/10.3233/JAD-2010-1240] [PMID: 20110594]
[51]
Zverova M, Kitzlerova E, Fisar Z, et al. Interplay between the APOE genotype and possible plasma biomarkers in Alzheimer’s disease. Curr Alzheimer Res 15(10): 938-50. (2018).
[http://dx.doi.org/10.2174/1567205015666180601090533] [PMID: 29852871]
[http://dx.doi.org/10.2174/1567205015666180601090533] [PMID: 29852871]
[52]
Durazzo TC, Mattsson N, Weiner MW. Interaction of cigarette smoking history with APOE genotype and age on amyloid level, glucose metabolism, and neurocognition in cognitively normal elders. Nicotine Tob Res 18(2): 204-11. (2016).
[http://dx.doi.org/10.1093/ntr/ntv075] [PMID: 25847292]
[http://dx.doi.org/10.1093/ntr/ntv075] [PMID: 25847292]
[53]
Qizilbash N, Gregson J, Johnson ME, et al. BMI and risk of dementia in two million people over two decades: a retrospective cohort study. Lancet Diabetes Endocrinol 3(6): 431-6. (2015).
[http://dx.doi.org/10.1016/S2213-8587(15)00033-9] [PMID: 25866264]
[http://dx.doi.org/10.1016/S2213-8587(15)00033-9] [PMID: 25866264]
[54]
Shin HY, Kim SW, Kim JM, Shin IS, Yoon JS. Association of grip strength with dementia in a Korean older population. Int J Geriatr Psychiatry 27(5): 500-5. (2012).
[http://dx.doi.org/10.1002/gps.2742] [PMID: 21626570]
[http://dx.doi.org/10.1002/gps.2742] [PMID: 21626570]
[55]
Hu G, Horswell R, Wang Y, et al. Body mass index and the risk of dementia among Louisiana low income diabetic patients. PLoS One 7(9): e44537 (2012).
[http://dx.doi.org/10.1371/journal.pone.0044537] [PMID: 22957079]
[http://dx.doi.org/10.1371/journal.pone.0044537] [PMID: 22957079]
[56]
Emmerzaal TL, Kiliaan AJ, Gustafson DR. 2003-2013: a decade of body mass index, Alzheimer’s disease, and dementia. J Alzheimers Dis 43(3): 739-55. (2015).
[http://dx.doi.org/10.3233/JAD-141086] [PMID: 25147111]
[http://dx.doi.org/10.3233/JAD-141086] [PMID: 25147111]
[57]
Craft S, Watson GS. Insulin and neurodegenerative disease: shared and specific mechanisms. Lancet Neurol 3(3): 169-78. (2004).
[http://dx.doi.org/10.1016/S1474-4422(04)00681-7] [PMID: 14980532]
[http://dx.doi.org/10.1016/S1474-4422(04)00681-7] [PMID: 14980532]
[58]
Rodríguez-Rodríguez E, Sánchez-Juan P, Vázquez-Higuera JL, et al. Genetic risk score predicting accelerated progression from mild cognitive impairment to Alzheimer’s disease. J Neural Transm (Vienna) 120(5): 807-12. (2013).
[http://dx.doi.org/10.1007/s00702-012-0920-x] [PMID: 23180304]
[http://dx.doi.org/10.1007/s00702-012-0920-x] [PMID: 23180304]
[59]
Carrasquillo MM, Crook JE, Pedraza O, et al. Late-onset Alzheimer’s risk variants in memory decline, incident mild cognitive impairment, and Alzheimer’s disease. Neurobiol Aging 36(1): 60-7. (2015).
[http://dx.doi.org/10.1016/j.neurobiolaging.2014.07.042] [PMID: 25189118]
[http://dx.doi.org/10.1016/j.neurobiolaging.2014.07.042] [PMID: 25189118]
[60]
Le Guennec K, Nicolas G, Quenez O, et al. ABCA7 rare variants and Alzheimer disease risk. Neurology 86(23): 2134-7. (2016).
[http://dx.doi.org/10.1212/WNL.0000000000002627] [PMID: 27037229]
[http://dx.doi.org/10.1212/WNL.0000000000002627] [PMID: 27037229]
[61]
Sassi C, Nalls MA, Ridge PG, et al. ABCA7 p.G215S as potential protective factor for Alzheimer’s disease. Neurobiol Aging 46: 235.e1-9. (2016).
[http://dx.doi.org/10.1016/j.neurobiolaging.2016.04.004] [PMID: 27289440]
[http://dx.doi.org/10.1016/j.neurobiolaging.2016.04.004] [PMID: 27289440]
[62]
De Roeck A, Van den Bossche T, van der Zee J, et al. Deleterious ABCA7 mutations and transcript rescue mechanisms in early onset Alzheimer’s disease. Acta Neuropathol 134(3): 475-87. (2017).
[http://dx.doi.org/10.1007/s00401-017-1714-x] [PMID: 28447221]
[http://dx.doi.org/10.1007/s00401-017-1714-x] [PMID: 28447221]
[63]
Moreno-Grau S, Rodríguez-Gómez O, Sanabria Á, et al. Exploring APOE genotype effects on Alzheimer’s disease risk and amyloid β burden in individuals with subjective cognitive decline: The FundacioACE Healthy Brain Initiative (FACEHBI) study baseline results. Alzheimers Dement 14(5): 634-43. (2018).
[http://dx.doi.org/10.1016/j.jalz.2017.10.005] [PMID: 29156223]
[http://dx.doi.org/10.1016/j.jalz.2017.10.005] [PMID: 29156223]
[64]
Heinsinger MN, William RG. Alzheimer’s disease genetic risk factor APOE-ε4 also affects normal brain function. Curr Alzheimer Res 11: 1200-7. (2016).
[65]
Hu P, Qin YH, Jing CX, Lu L, Hu B, Du PF. Does the geographical gradient of ApoE4 allele exist in China? A systemic comparison among multiple Chinese populations. Mol Biol Rep 38(1): 489-94. (2011).
[http://dx.doi.org/10.1007/s11033-010-0132-0] [PMID: 20354905]
[http://dx.doi.org/10.1007/s11033-010-0132-0] [PMID: 20354905]
[66]
Liang S, Pan M, Geng HH, et al. Apolipoprotein E polymorphism in normal Han Chinese population: frequency and effect on lipid parameters. Mol Biol Rep 36(6): 1251-6. (2009).
[http://dx.doi.org/10.1007/s11033-008-9305-5] [PMID: 18600472]
[http://dx.doi.org/10.1007/s11033-008-9305-5] [PMID: 18600472]
[67]
Jun G, Naj AC, Beecham GW, et al. Meta-analysis confirms CR1, CLU, and PICALM as Alzheimer disease risk loci and reveals interactions with APOE genotypes. Arch Neurol 67(12): 1473-84. (2010).
[http://dx.doi.org/10.1001/archneurol.2010.201] [PMID: 20697030]
[http://dx.doi.org/10.1001/archneurol.2010.201] [PMID: 20697030]