
School of Medicine Publications and Presentations
Document Type
Article
Publication Date
3-2025
Abstract
Background: Effect of apolipoprotein E (APOE) on Alzheimer's disease and related dementias (ADRD) risk is heterogeneous across populations, with scarce data on Hispanics/Latinos.
Methods: APOE genotype was studied in 12,221 Hispanics/Latinos (per cohort and via metanalysis): Caribbean-Hispanics, Mexicans, Mexican-Americans, and Peruvians/Bolivians. A subsample had longitudinal assessment and plasma p-tau. We tested the modifying effects of global and local ancestries. Results were replicated in an independent Peruvian cohort and brain samples.
Results: APOE ε4 effect was strongest in Peruvians/Bolivians (odds ratio [OR] = 6.13, 95% confidence interval [CI] = 2.71-13.83), followed by Mexicans (OR = 4.31, 95% CI = 1.58-11.74), Mexican-Americans (OR = 3.06, 95% CI = 2.04-4.59), and Caribbean-Hispanics (OR = 2.22, 95% CI = 1.99-2.48). Meta-analyses showed OR = 2.32 (95% CI = 2.09-2.57) and OR = 0.81 (95% CI = 0.68-0.97) for the ε4 and ε2 allele, respectively. The APOE ε4 effect was replicated independently in Peruvians (OR = 5.06, 95% CI = 2.48-10.70). ε4 carriers displayed higher ADRD conversions and p-tau levels. Global and local ancestries did not modify ADRD risk, and they were associated with Braak stage.
Discussion: APOE shows a heterogeneous effect on ADRD risk in our Hispanics/Latinos sample, the largest to date.
Highlights: The apolipoprotein E (APOE) ε4 effect is stronger in Peruvians/Bolivians than in other Hispanic/Latino groups. The strong APOE effect size in Peruvians and Bolivians was replicated in a second independent Peruvian cohort. Meta-analysis for ε4 and ε2 confirmed a significant association with Alzheimer's disease and related dementias (ADRD). Global and local ancestry do not modify the association between APOE genotype and ADRD.
Recommended Citation
Barral, S., Yang, Z., Phillips, N., Barber, R. C., Brickman, A. M., Honig, L. S., Cieza, B., Reyes-Dumeyer, D., Mayeux, R., Rajabli, F., Cuccaro, M. L., Vance, J. M., Arango, S. M., Samper-Ternent, R., Obregon, A. M., Montesinos, R., Soto-Añari, M., Duran, J. C., Cusicanqui, M., Velazquez, I. Z. J., … Tosto, G. (2025). APOE and Alzheimer's disease and related dementias risk among 12,221 Hispanics/Latinos. Alzheimer's & dementia : the journal of the Alzheimer's Association, 21(4), e70138. https://doi.org/10.1002/alz.70138
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Publication Title
Alzheimer's & dementia
DOI
10.1002/alz.70138
Academic Level
faculty
Mentor/PI Department
Neuroscience
Comments
© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.