Alzheimer's polygenic hazard score in SuperAgers: SuperGenes or SuperResilience?

SuperAgers are individuals over age 80 with superior episodic memory, at a level consistent with individuals 20 to 30 years their junior and who seem to show resistance to age-related neurofibrillary degeneration. Here we examine whether low genetic risk for Alzheimer's disease (AD) contributes to SuperAgers' unusually high episodic memory performance in advanced age. The AD polygenic hazard score (PHS) was calculated for each SuperAger and cognitively normal participant and compared between groups. A total of 37 SuperAgers (73% female, mean [standard deviation] 82.7 [2.8] years old) and 35 controls (54% female, 83.7 [4.3] years old) were included. There was no significant difference in the AD PHS between SuperAgers and cognitively normal controls. Unusually successful cognitive aging cannot be simply explained by low polygenic risk for AD as assessed by common genetic variants. However, rare variants and common protective genetic factors may contribute to resistance or resilience. SuperAging cannot be simply explained by low polygenic risk for Alzheimer's disease.Rare variants and common protective genetic factors may contribute to SuperAging.A protective factors polygenic score may uncover mechanisms for SuperAging.

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© 2022 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Déclaration de conflit d'intérêts

Authors Emily Rogalski, Sarah J. Banks, Sandra Weintraub, James B. Brewer, M.‐Marsel Mesulam, Barbara E. Spencer, Anders M. Dale, and Changiz Geula receive grant support from NIH. Anders M. Dale is a founder of and holds equity interest in CorTechs Labs, La Jolla, California, and serves on its scientific advisory board. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies. Dr. James B. Brewer has served on advisory boards for Elan, Bristol‐Myers Squibb, Avanir, Novartis, Genentech, and Eli Lilly and holds stock options in CorTechs Labs, Inc. and Human Longevity, Inc. Ms. Beth Makowski‐Woidan reports no conflicts. Author disclosures are available in the supporting information.