Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 May:101:298.e11-298.e15.
doi: 10.1016/j.neurobiolaging.2020.10.003. Epub 2020 Dec 10.

Dissecting the role of Amerindian genetic ancestry and the ApoE ε4 allele on Alzheimer disease in an admixed Peruvian population

Maria Victoria Marca-Ysabel  1 , Farid Rajabli  2 , Mario Cornejo-Olivas  3 , Patrice G Whitehead  2 , Natalia K Hofmann  2 , Maryenela Zaida Illanes Manrique  1 , Diego Martin Veliz Otani  4 , Ana Karina Milla Neyra  1 , Sheila Castro Suarez  5 , Maria Meza Vega  6 , Larry D Adams  2 , Pedro R Mena  2 , Isasi Rosario  7 , Michael L Cuccaro  7 , Jeffery M Vance  7 , Gary W Beecham  7 , Nilton Custodio  8 , Rosa Montesinos  8 , Pilar E Mazzetti Soler  9 , Margaret A Pericak-Vance  10
Affiliations

Dissecting the role of Amerindian genetic ancestry and the ApoE ε4 allele on Alzheimer disease in an admixed Peruvian population

Maria Victoria Marca-Ysabel et al. Neurobiol Aging. 2021 May.

Abstract

Alzheimer disease (AD) is the leading cause of dementia in the elderly and occurs in all ethnic and racial groups. The apolipoprotein E (ApoE) ε4 is the most significant genetic risk factor for late-onset AD and shows the strongest effect among East Asian populations followed by non-Hispanic white populations and has a relatively lower effect in African descent populations. Admixture analysis in the African American and Puerto Rican populations showed that the variation in ε4 risk is correlated with the genetic ancestral background local to the ApoE gene. Native American populations are substantially underrepresented in AD genetic studies. The Peruvian population with up to ~80 of Amerindian (AI) ancestry provides a unique opportunity to assess the role of AI ancestry in AD. In this study, we assess the effect of the ApoE ε4 allele on AD in the Peruvian population. A total of 79 AD cases and 128 unrelated cognitive healthy controls from Peruvian population were included in the study. Genome-wide genotyping was performed using the Illumina Global screening array v2.0. Global ancestry and local ancestry analyses were assessed. The effect of the ApoE ε4 allele on AD was tested using a logistic regression model by adjusting for age, gender, and population substructure (first 3 principal components). Results showed that the genetic ancestry surrounding the ApoE gene is predominantly AI (60.6%) and the ε4 allele is significantly associated with increased risk of AD in the Peruvian population (odds ratio = 5.02, confidence interval: 2.3-12.5, p-value = 2e-4). Our results showed that the risk for AD from ApoE ε4 in Peruvians is higher than we have observed in non-Hispanic white populations. Given the high admixture of AI ancestry in the Peruvian population, it suggests that the AI genetic ancestry local to the ApoE gene is contributing to a strong risk for AD in ε4 carriers. Our data also support the findings of an interaction between the genetic risk allele ApoE ε4 and the ancestral backgrounds located around the genomic region of ApoE gene.

Keywords: Alzheimer disease (AD); Amerindian (AI) genetic ancestry; Apolipoprotein E (ApoE).

PubMed Disclaimer

Conflict of interest statement

Disclosure Statement

  1. No conflicts of interest exist

  2. No contracts relating to this research

  3. No agreements that could be involved in a financial interest

Figures

Figure 1.
Figure 1.
The boxplot of the four parental ancestries in Peruvian dataset (A). Bar-plot of four-way admixed Peruvian individuals estimated using ADMIXTURE software at K = 4 (B)
See this image and copyright information in PMC

References

    1. Aleshkov S, Abraham CR, Zannis VI 1997. Interaction of nascent apoE2, apoE3, and apoE4 isoforms expressed in mammalian cells with amyloid peptide b(1–40). Relevance to Alzheimer’s disease. Biochemistry 36(34), 10571–10580. - PubMed
    1. Alexander DH, Novembre J, Lange K 2009. Fast model-based estimation of ancestry in unrelated individuals. Genome Research 19,1655–1664. - PMC - PubMed
    1. Alzheimer’s Association 2011. Alzheimer’s disease facts and figures. Alzheimer’s Dementia 7, 20–21 - PubMed
    1. Alzheimer’s Disease, C., Pilotto A, Bullido MJ, Peters O, Crane PK, Bennett D, Bosco P, Coto E, Boccardi V, De Jager PL, Lleo A, Warner N, Lopez OL, Ingelsson M, Deloukas P, Cruchaga C, Graff C, Gwilliam R, Fornage M, Goate AM, Sanchez-Juan P, Kehoe PG, Amin N, Ertekin-Taner N, Berr C, Debette S, Love S, Launer LJ, Younkin SG, Dartigues JF, Corcoran C, Ikram MA, Dickson DW, Nicolas G, Campion D, Tschanz J, Schmidt H, Hakonarson H, Clarimon J, Munger R, Schmidt R, Farrer LA, Van Broeckhoven C, M COD, DeStefano AL, Jones L, Haines JL, Deleuze JF, Owen MJ, Gudnason V, Mayeux R, Escott-Price V, Psaty BM, Ramirez A, Wang LS, Ruiz A, van Duijn CM, Holmans PA, Seshadri S, Williams J, Amouyel P, Schellenberg GD, Lambert JC, Pericak-Vance MA, 2019. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Abeta, tau, immunity and lipid processing. Nat Genet 51(3), 414–430. - PMC - PubMed
    1. Blue EE, Horimoto AR, Mukherjee S, Wijsman EM, Thornton TA 2019. Local ancestry at APOE modifies Alzheimer’s disease risk in Caribbean Hispanics. Alzheimer’s & Dementia 15(12),1524–1532. - PMC - PubMed

Publication types

Substances