African ancestry protects against Alzheimer's disease-related neuropathology

D Schlesinger, L T Grinberg, J G Alba, M S Naslavsky, L Licinio, J M Farfel, C K Suemoto, R E de Lucena Ferretti, R E P Leite, M P de Andrade, A C F dos Santos, H Brentani, C A Pasqualucci, R Nitrini, W Jacob-Filho, M Zatz, Brazilian Aging Brain Study Group, D Schlesinger, L T Grinberg, J G Alba, M S Naslavsky, L Licinio, J M Farfel, C K Suemoto, R E de Lucena Ferretti, R E P Leite, M P de Andrade, A C F dos Santos, H Brentani, C A Pasqualucci, R Nitrini, W Jacob-Filho, M Zatz, Brazilian Aging Brain Study Group

Abstract

Previous studies in dementia epidemiology have reported higher Alzheimer's disease rates in African-Americans when compared with White Americans. To determine whether genetically determined African ancestry is associated with neuropathological changes commonly associated with dementia, we analyzed a population-based brain bank in the highly admixed city of São Paulo, Brazil. African ancestry was estimated through the use of previously described ancestry-informative markers. Risk of presence of neuritic plaques, neurofibrillary tangles, small vessel disease, brain infarcts and Lewy bodies in subjects with significant African ancestry versus those without was determined. Results were adjusted for multiple environmental risk factors, demographic variables and apolipoprotein E genotype. African ancestry was inversely correlated with neuritic plaques (P=0.03). Subjects with significant African ancestry (n=112, 55.4%) showed lower prevalence of neuritic plaques in the univariate analysis (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.55-0.95, P=0.01) and when adjusted for age, sex, APOE genotype and environmental risk factors (OR 0.43, 95% CI 0.21-0.89, P=0.02). There were no significant differences for the presence of other neuropathological alterations. We show for the first time, using genetically determined ancestry, that African ancestry may be highly protective of Alzheimer's disease neuropathology, functioning through either genetic variants or unknown environmental factors. Epidemiological studies correlating African-American race/ethnicity with increased Alzheimer's disease rates should not be interpreted as surrogates of genetic ancestry or considered to represent African-derived populations from the developing nations such as Brazil.

Figures

Figure 1
Figure 1
Individual African ancestry estimates according to self-declared race in Brazil.
Figure 2
Figure 2
Odds ratio of neuropathological alterations.
Figure 3
Figure 3
Odds ratio of presence of neuritic plaques, comparing African with non-African ancestry, adjusted for age and sex; age, sex and APOE4 status; and all factors.

References

    1. Parra FC, Amado RC, Lambertucci JR, Rocha J, Antunes CM, Pena SD. Color and genomic ancestry in Brazilians. Proc Natl Acad Sci USA. 2003;100:177–182.
    1. Davis FJ.Who is Black?: One Nation's Definition10th anniversary ed. Pennsylvania State University Press: University Park, PA; 2001
    1. Mörner M. Race Mixture in the History of Latin America. Little: University Park, PA; 1967.
    1. Shriver MD, Parra EJ, Dios S, Bonilla C, Norton H, Jovel C, et al. Skin pigmentation, biogeographical ancestry and admixture mapping. Hum Genet. 2003;112:387–399.
    1. Anderson NB, Bulatao RA, Cohen B, National Research Council (U.S.). Panel on Race Ethnicity and Health in Later Life . Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. National Academies Press: Washington, DC; 2004.
    1. Cooper RS, Kaufman JS, Ward R. Race and genomics. N Engl J Med. 2003;348:1166–1170.
    1. Matthews FE, Brayne C, Lowe J, McKeith I, Wharton SB, Ince P. Epidemiological pathology of dementia: attributable-risks at death in the Medical Research Council Cognitive Function and Ageing Study. PLoS Med. 2009;6:e1000180.
    1. Demirovic J, Prineas R, Loewenstein D, Bean J, Duara R, Sevush S, et al. Prevalence of dementia in three ethnic groups: the South Florida program on aging and health. Ann Epidemiol. 2003;13:472–478.
    1. Froehlich TE, Bogardus ST, Inouye SK. Dementia and race: are there differences between African Americans and Caucasians. J Am Geriatr Soc. 2001;49:477–484.
    1. Hou CE, Yaffe K, Pérez-Stable EJ, Miller BL. Frequency of dementia etiologies in four ethnic groups. Dement Geriatr Cogn Disord. 2006;22:42–47.
    1. Schoenberg BS, Anderson DW, Haerer AF. Severe dementia. Prevalence and clinical features in a biracial US population. Arch Neurol. 1985;42:740–743.
    1. Heyman A, Fillenbaum G, Prosnitz B, Raiford K, Burchett B, Clark C. Estimated prevalence of dementia among elderly black and white community residents. Arch Neurol. 1991;48:594–598.
    1. Tishkoff SA, Reed FA, Friedlaender FR, Ehret C, Ranciaro A, Froment A, et al. The genetic structure and history of Africans and African Americans. Science. 2009;324:1035–1044.
    1. Bravata DM, Wells CK, Gulanski B, Kernan WN, Brass LM, Long J, et al. Racial disparities in stroke risk factors: the impact of socioeconomic status. Stroke. 2005;36:1507–1511.
    1. Cook BL, Manning WG. Measuring racial/ethnic disparities across the distribution of health care expenditures. Health Serv Res. 2009;44:1603–1621.
    1. Kaufman JS, Cooper RS, McGee DL. Socioeconomic status and health in blacks and whites: the problem of residual confounding and the resiliency of race. Epidemiology. 1997;8:621–628.
    1. Pytel P. Vascular and Alzheimer-type pathology in an autopsy study of African-Americans. Neurology. 2006;66:433–435.
    1. Riudavets MA, Rubio A, Cox C, Rudow G, Fowler D, Troncoso JC. The prevalence of Alzheimer neuropathologic lesions is similar in blacks and whites. J Neuropathol Exp Neurol. 2006;65:1143–1148.
    1. Wilkins CH, Grant EA, Schmitt SE, McKeel DW, Morris JC. The neuropathology of Alzheimer disease in African American and white individuals. Arch Neurol. 2006;63:87–90.
    1. Fejerman L, John EM, Huntsman S, Beckman K, Choudhry S, Perez-Stable E, et al. Genetic ancestry and risk of breast cancer among U.S. Latinas. Cancer Res. 2008;68:9723–9728.
    1. Kumar R, Seibold MA, Aldrich MC, Williams LK, Reiner AP, Colangelo L, et al. Genetic ancestry in lung-function predictions. N Engl J Med. 2010;363:321–330.
    1. Cunha MCd, Salzano FM. História dos índios no Brasil. São Paulo, SP: Fundação de Amparo à Pesquisa do Estado de São Paulo: Companhia das Letras: Secretaria Municipal de Cultura, Prefeitura do Município de São Paulo. Companhia das Letras: São Paulo; 1992.
    1. Hall GM. Slavery and African Ethnicities in the Americas: Restoring the Links. University of North Carolina Press: Chapel Hill; 2005.
    1. Basto FLdB.Síntese da História da Imigração no Brasil2 edn. sn: Rio de Janeiro, Brasil; 1998
    1. Lins TC, Vieira RG, Abreu BS, Grattapaglia D, Pereira RW. Genetic composition of Brazilian population samples based on a set of twenty-eight ancestry informative SNPs. Am J Hum Biol. 2009;22:187–192.
    1. Pena SD, Bastos-Rodrigues L, Pimenta JR, Bydlowski SP. DNA tests probe the genomic ancestry of Brazilians. Braz J Med Biol Res. 2009;42:870–876.
    1. Grinberg LT, Ferretti RE, Farfel JM, Leite R, Pasqualucci CA, Rosemberg S, et al. Brazilian Aging Brain Study Group Brain bank of the Brazilian aging brain study group—a milestone reached and more than 1,600 collected brains. Cell Tissue Bank. 2007;8:151–162.
    1. Ferretti R, Damin A, Brucki S, Morillo L, Perroco T, Campora F, et al. Post-Mortem diagnosis of dementia by informant interview. Dement Neuropsychol. 2010;4:138–144.
    1. Jorm AF, Jacomb PA. The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): socio-demographic correlates, reliability, validity and some norms. Psychol Med. 1989;19:1015–1022.
    1. Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology. 1993;43:2412–2414.
    1. Mirra SS. The CERAD neuropathology protocol and consensus recommendations for the postmortem diagnosis of Alzheimer's disease: a commentary. Neurobiol Aging. 1997;18:S91–SS4.
    1. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82:239–259.
    1. McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA, et al. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology. 1996;47:1113–1124.
    1. Nassir R, Kosoy R, Tian C, White PA, Butler LM, Silva G, et al. An ancestry informative marker set for determining continental origin: validation and extension using human genome diversity panels. BMC Genet. 2009;10:39.
    1. Calero O, Hortiguela R, Bullido MJ, Calero M. Apolipoprotein E genotyping method by real time PCR, a fast and cost-effective alternative to the TaqMan and FRET assays. J Neurosci Methods. 2009;183:238–240.
    1. Li JZ, Absher DM, Tang H, Southwick AM, Casto AM, Ramachandran S, et al. Worldwide human relationships inferred from genome-wide patterns of variation. Science. 2008;319:1100–1104.
    1. HapMap A haplotype map of the human genome. Nature. 2005;437:1299–12320.
    1. Pritchard JK, Stephens M, Donnelly P. Inference of population structure using multilocus genotype data. Genetics. 2000;155:945–959.
    1. Ogunniyi A, Baiyewu O, Gureje O, Hall KS, Unverzagt F, Siu SH, et al. Epidemiology of dementia in Nigeria: results from the Indianapolis-Ibadan study. Eur J Neurol. 2000;7:485–490.
    1. Chiu M, Austin PC, Manuel DG, Tu JV. Comparison of cardiovascular risk profiles among ethnic groups using population health surveys between 1996 and 2007. Can Med Assoc J. 2010;182:E301–EE10.
    1. Schwamm LH, Reeves MJ, Pan W, Smith EE, Frankel MR, Olson D, et al. Race/ethnicity, quality of care, and outcomes in ischemic stroke. Circulation. 2010;121:1492–1501.
    1. Race, Ethnicity, and Genetics Working Group The use of racial, ethnic, and ancestral categories in human genetics research. Am J Hum Genet. 2005;77:519–532.
    1. Kidd J, Friedlaender F, Speed W, Pakstis A, De La Vega F, Kidd K. Analyses of a set of 128 ancestry informative single-nucleotide polymorphisms in a global set of 119 population samples. Invest Genet. 2011;2:1.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する