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

Alejandro Caceres; Aina Jene; Tonu Esko; Luis A. Perez-Jurado; Juan R. Gonzalez

doi:10.1016/j.neurobiolaging.2020.02.003

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

Alejandro Caceres, Aina Jene, Tonu Esko, Luis A. Perez-Jurado, Juan R. Gonzalez

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

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 (OR_{EDY × 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.

Original language	English
Pages (from-to)	150.e1-150.e4
Journal	Neurobiology of Aging
Volume	90
DOIs	https://doi.org/10.1016/j.neurobiolaging.2020.02.003
Publication status	Published or Issued - Jun 2020

Keywords

Aging
Alzheimer's disease
Chromosome Y
Mosaicism
RNA sequencing
Transcriptomics

ASJC Scopus subject areas

General Neuroscience
Ageing
Clinical Neurology
Developmental Biology
Geriatrics and Gerontology

Access to Document

10.1016/j.neurobiolaging.2020.02.003

Cite this

@article{a2d29e6eae5d4241b4ad0ac69d9327c6,

title = "Extreme downregulation of chromosome Y and Alzheimer's disease in men",

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.",

keywords = "Aging, Alzheimer's disease, Chromosome Y, Mosaicism, RNA sequencing, Transcriptomics",

author = "Alejandro Caceres and Aina Jene and Tonu Esko and Perez-Jurado, {Luis A.} and Gonzalez, {Juan R.}",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = jun,

doi = "10.1016/j.neurobiolaging.2020.02.003",

language = "English",

volume = "90",

pages = "150.e1--150.e4",

journal = "Neurobiology of Aging",

issn = "0197-4580",

publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Extreme downregulation of chromosome Y and Alzheimer's disease in men

AU - Caceres, Alejandro

AU - Jene, Aina

AU - Esko, Tonu

AU - Perez-Jurado, Luis A.

AU - Gonzalez, Juan R.

PY - 2020/6

Y1 - 2020/6

N2 - 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.

AB - 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.

KW - Aging

KW - Alzheimer's disease

KW - Chromosome Y

KW - Mosaicism

KW - RNA sequencing

KW - Transcriptomics

UR - http://www.scopus.com/inward/record.url?scp=85080992837&partnerID=8YFLogxK

U2 - 10.1016/j.neurobiolaging.2020.02.003

DO - 10.1016/j.neurobiolaging.2020.02.003

M3 - Article

C2 - 32147245

AN - SCOPUS:85080992837

SN - 0197-4580

VL - 90

SP - 150.e1-150.e4

JO - Neurobiology of Aging

JF - Neurobiology of Aging

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Cite this