Clonal Hematopoiesis is Associated With Protection From Alzheimer's Disease

Authors

Hind Bouzid
Julia A Belk
Max Jan
Yanyan Qi
Chloé Sarnowski
Sara Wirth
Lisa Ma
Matthew R Chrostek
Herra Ahmad
Daniel Nachun
Winnie Yao
Alexa Beiser
Alexander G Bick
Joshua C Bis
Myriam Fornage
William T Longstreth
Oscar L Lopez
Pradeep Natarajan
Bruce M Psaty
Claudia L Satizabal
Joshua Weinstock
Eric B Larson
Paul K Crane
C Dirk Keene
Sudha Seshadri
Ansuman T Satpathy
Thomas J Montine
Siddhartha Jaiswal

Publication Date

7-1-2023

Journal

Nature Medicine

Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) is a premalignant expansion of mutated hematopoietic stem cells. As CHIP-associated mutations are known to alter the development and function of myeloid cells, we hypothesized that CHIP may also be associated with the risk of Alzheimer's disease (AD), a disease in which brain-resident myeloid cells are thought to have a major role. To perform association tests between CHIP and AD dementia, we analyzed blood DNA sequencing data from 1,362 individuals with AD and 4,368 individuals without AD. Individuals with CHIP had a lower risk of AD dementia (meta-analysis odds ratio (OR) = 0.64, P = 3.8 × 10

Keywords

Humans, Clonal Hematopoiesis, Alzheimer Disease, Hematopoiesis, Hematopoietic Stem Cells, Precancerous Conditions, Mutation