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.

Mixed pathology is more likely in black than white decedents with Alzheimer dementia

“…While the primary result was that African ancestry is protective of AD pathology, there was also a tendency of higher odds of Lewy body pathology in persons of African ancestry; however, it did not reach significance and was not a major focus of the article. 23 The high frequency of Lewy body pathology among black decedents in our sample may reflect a selection bias for clinic samples. Lewy body disease, with and without coexisting AD pathology, is associated more with behavioral abnormalities, such as hallucinations and REM sleep behavior disorder, than clinical AD.…”

Higher Prevalence of TDP‐43 Proteinopathy in Cognitively Normal Asians: A Clinicopathological Study on a Multiethnic Sample

“…These studies focused mainly on highly educated Caucasian subjects with an average age of death of over 70 years. The study participants investigated in the present study were relatively younger, had a greater range of exposure to education, (22) and came from an ethnically diverse city (58). The slightly lower prevalence of TDP-43 proteinopathy observed in our series may reflect the lower age of the study subjects, because TDP-43 pathology is more prevalent in older individuals (6, 27).…”

Amerindian Genetic Ancestry Protects against Alzheimer’s Disease

“…Also, Rosenberg et al [30] found that persons with a greater degree of Cherokee Indian heritage had a lower risk of developing AD. Until now, one single report sought to investigate the relationship between genomic ancestry and the AD phenotype in Brazil [31]. According to their report, African ancestry protects against AD-related neuropathology.…”