title: African ancestry protects against Alzheimer's disease-related neuropathology.
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.
authors: Human Genome Research Center, University of São Paulo, São Paulo, Brazil. dschles@einstein.br
authors: D
authors: D
authors: Schlesinger
authors: L T
authors: LT
authors: Grinberg
authors: J G
authors: JG
authors: Alba
authors: M S
authors: MS
authors: Naslavsky
authors: L
authors: L
authors: Licinio
authors: J M
authors: JM
authors: Farfel
authors: C K
authors: CK
authors: Suemoto
authors: R E
authors: RE
authors: de Lucena Ferretti
authors: R E P
authors: RE
authors: Leite
authors: M P
authors: MP
authors: de Andrade
authors: A C F
authors: AC
authors: dos Santos
authors: H
authors: H
authors: Brentani
authors: C A
authors: CA
authors: Pasqualucci
authors: R
authors: R
authors: Nitrini
authors: W
authors: W
authors: Jacob-Filho
authors: M
authors: M
authors: Zatz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D044383:Black People / Q000235:genetics*; D020520:Brain Infarction / Q000209:etiology / Q000235:genetics; D001938:Brazil / Q000453:epidemiology / Q000208:ethnology; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000209:etiology* / Q000235:genetics*; D016874:Neurofibrillary Tangles / Q000473:pathology; D016017:Odds Ratio; D058225:Plaque, Amyloid / Q000473:pathology; D012189:Retrospective Studies; D012307:Risk Factors; D018709:Statistics, Nonparametric; D001741:Black or African American
chemical_list: D001057:Apolipoproteins E