Extreme downregulation of chromosome Y and Alzheimer's disease in men.

Neurobiology of Aging
Alejandro CáceresJuan R González

Abstract

Research has revealed scarcely any biological factors of Alzheimer's disease (AD) that are specific to men. Here, we found that the extreme downregulation of chromosome Y (EDY) increases the age-related risk of AD in men. We considered that EDY was a possible male-specific pathway toward AD because EDY is the most likely consequence of the mosaic loss of chromosome Y, which has been recently associated with AD. We studied EDY in the undiseased brain of 371 individuals and observed that it co-occurred across multiple brain regions (p < 10-4) and associated with rs114241159 (p = 1.53 × 10-7) within ACSS3/PPFIA2, previously linked to amyloid beta concentrations. We also analyzed the 5 largest transcriptomic case-control studies, publicly available to date on AD (cases/controls = 556/462) and found a significant interaction with age (OREDY × age = 1.22, p = 0.0038). Our analyses suggest that aging men who live longer by avoiding EDY are more resilient to AD than those who do not.

Citations

Feb 2, 2021·Haematologica·Panagiotis Baliakas, Lars A Forsberg
Mar 27, 2021·Mechanisms of Ageing and Development·Julie A Chowen, Luis M Garcia-Segura
Apr 11, 2021·Cellular and Molecular Life Sciences : CMLS·Jan P DumanskiLars A Forsberg
Apr 27, 2021·Biological Psychiatry·Lei GuoDongming Cai
Jul 28, 2021·Scientific Reports·Jonas MattissonLars A Forsberg

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