Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
APOE and Alzheimer's disease and related dementias risk among 12,221 Hispanics/Latinos.
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Barral Sandra, Yang Zikun, Phillips Nicole, Barber Robert C, Brickman Adam M, Honig Lawrence S, Cieza Basilio, Reyes-Dumeyer Dolly, Mayeux Richard, Rajabli Farid, Cuccaro Michael L, Vance Jeffery M, Arango Silvia Mejia, Samper-Ternent Rafael, Obregon Alejandra Michaels, Montesinos Rosa, Soto-Añari Marcio, Duran Juan Carlos, Cusicanqui Maria, Velazquez Ivonne Z Jimenez, Marca Victoria, Illanes-Manrique Maryenela, Cornejo-Olivas Mario, Pericak-Vance Margaret, Wong Rebeca, O'Bryant Sid, Custodio Nilton, Tosto Giuseppe
Аннотация
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.
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.