Increased genetic protection against Alzheimer’s disease in centenarians
Harold Bae (Oregon State University)
Zeyuan Song (Tufts University School of Medicine, Tufts Medical Center)
Amanat Ali (Albert Einstein College of Medicine of Yeshiva University)
Niccolò Tesi (TU Delft - Pattern Recognition and Bioinformatics, Amsterdam UMC, Vrije Universiteit Amsterdam)
Marc Hulsman (Amsterdam UMC, Vrije Universiteit Amsterdam, TU Delft - Pattern Recognition and Bioinformatics)
Sven van der Lee (Vrije Universiteit Amsterdam, Amsterdam UMC, TU Delft - Pattern Recognition and Bioinformatics)
Natasja M. van Schoor (Vrije Universiteit Amsterdam, TU Delft - Pattern Recognition and Bioinformatics)
Marcel Reinders (TU Delft - Pattern Recognition and Bioinformatics)
Henne Holstege (Amsterdam UMC, TU Delft - Intelligent Systems, Vrije Universiteit Amsterdam)
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Abstract
We constructed a polygenic protective score specific to Alzheimer’s disease (AD PPS) based on the current literature among the participants enrolled in five studies of healthy aging and extreme longevity in the USA, Europe, and Asia. This AD PPS did not include variants on apolipoprotein E (APOE) gene. Comparisons of AD PPS in different data sets of healthy agers and centenarians showed that centenarians have stronger genetic protection against AD compared to individuals without familial longevity. The current study also shows evidence that this genetic protection increases with increasingly older ages in centenarians (centenarians who died before reaching age 105 years, semi-supercentenarians who reached age 105 to 109 years, and supercentenarians who reached age 110 years and older). However, the genetic protection was of modest size: the average increase in AD PPS was approximately one additional protective allele per 5 years of gained lifetime. Additionally, we show that the higher AD PPS was associated with better cognitive function and decreased mortality. Taken together, this analysis suggests that individuals who achieve the most extreme ages, on average, have the greatest protection against AD. This finding is robust to different genetic backgrounds with important implications for universal applicability of therapeutics that target this AD PPS.