Accès ouvert déclaré 2026 article

SuperAging is not the inverse of common-variant Alzheimer’s risk: evidence across genetic ancestries

Ignazio Stefano Piras, Ana Werneck Capuano, Amanda Cook Maher, Rhiana Schafer, Anna Bonfitto, Serena Song, Francis Taguinod, Felicia Goldstein, Angela Roberts, Ozioma C. Okonkwo, Adam Martersteck, AR Trammell, M Parker, L Kaddoura, G Harris, A Ellison, S Saleh, D Qui, H Ahmed, J Chung, Bobbi Stark, I Ayala, C Geula, M Mesulam, A Lim, RH Swartz, K Seibert, M Kharitonova, S McDermott, C Zolliecoffer, Elizabeth Addison, Hannah Peirce, J Engelmeyer, Phyllis Timpo, R Devine, Sophia Moore, H Whitmore, M McCarthy, Kianna Hearns, A Capuano, S Wang, E Rose, GA Lincoln, H Paulson, L Wathen, V Balog, Jordan R Bross, Johnathan Reader, A Bhaumik, K Warner, Y Sturt, Bill McIlroy, Karen Van Ooteghem, K Beyer, V Thai, C Dunne, K Doyle-Thomas, S Lose, A Pandos, M Bruce, V Uday, AC Roberts, E Finger, Ivan Culum, R Bartha, JB Orange, K Coleman, S Jesso, C Silveira, E Narayan, J Li, N Aulakh, Y Tuncel, B Haller, DO Ofori, A Cardaio, J El-Khoury, Matt Huentelman, Emily Rogalski

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Le résumé fourni par la source

As longevity increases and the population over age 65 expands, advancing age remains the most reliable predictor of cognitive decline, highlighting the need to identify biological mechanisms that support exceptional cognitive aging. We tested whether lower inherited risk of Alzheimer’s disease (AD) dementia predicts SuperAger status (adults ≥ 80 years with episodic memory at least as good as middle-age adults) using prospectively enrolled SuperAgers and Cognitively Average Controls (Controls) from the multisite SuperAging Research Initiative. We studied 231 participants (SuperAgers n = 142; Controls n = 89). We confirmed that the genetic ancestry structure across groups was comparable. We evaluated whether APOE status (ε2, ε3, ε4) and three AD polygenic risk scores (PRS) derived from large contemporary Genome-Wide Association Studies (GWAS) (PRS Lambert , PRS Wightman , PRS Bellenguez ) predicted SuperAging status using logistic regression models adjusted for age, sex, and education, considering ancestry interactions. APOE allele and genotype distributions did not differ between groups, and neither APOE nor any of the three PRS predicted SuperAger status. Results were unchanged when accounting for global non-European or African ancestry or principal components. In this well-characterized cohort, neither APOE nor contemporary PRS explained SuperAger status. These findings suggest that the exceptional late-life memory phenotype that is characteristic of SuperAging is not explained by common-variant AD genetic risk captured by APOE or contemporary AD PRS, motivating a deeper investigation of potential rare genetic variations and experiential factors contributing to exceptional cognitive aging.

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Le contrôle bibliographique ouvert

DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.

Titre Crossref: SuperAging is not the inverse of common-variant Alzheimer’s risk: evidence across genetic ancestries
Date Crossref: 23/07/2026
Éditeur: Springer Science and Business Media LLC
Type: journal-article

Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.

Où se fait cette recherche

Translational Genomics Research Institute Division of Early Detection and Prevention pays non établi dans la notice
Structure de recherche
University of Chicago Department of Neurology pays non établi dans la notice
Université ou école supérieure
University of Michigan Department of Psychiatry pays non établi dans la notice
Université ou école supérieure
Emory University Department of Neurology pays non établi dans la notice
Université ou école supérieure
Western University Department of Computer Science pays non établi dans la notice
Université ou école supérieure
University of Wisconsin–Madison pays non établi dans la notice
Université ou école supérieure
Alzheimer's Association pays non établi dans la notice
Organisation à but non lucratif
Arizona Alzheimer’s Consortium pays non établi dans la notice
Institution
Canadian Centre for Activity and Aging pays non établi dans la notice
Institution
School of Communication Sciences and Disorders pays non établi dans la notice
Université ou école supérieure
University of Wisconsin School of Medicine and Public Health Wisconsin Alzheimer's Disease Research Center and Department of Medicine pays non établi dans la notice
Université ou école supérieure

Division of Early Detection and Prevention — Translational Genomics Research Institute, Department of Neurology — University of Chicago et Department of Psychiatry — University of Michigan, avec 8 autres affiliations.

Une affiliation ne permet pas de déduire la nationalité d’un auteur.

Les sujets associés

Genetic Associations and EpidemiologyDementia and Cognitive Impairment ResearchCognitive Abilities and Testing

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