Genetically proxied IL-6 signaling and risk of Alzheimer's disease and lobar intracerebral hemorrhage: A drug target Mendelian randomization study.

ABSTRACT:

Introduction

Evidence suggests that higher C-reactive protein (CRP) is associated with lower risk of Alzheimer's disease (AD) and lobar intracerebral hemorrhage (ICH). Whether interleukin (IL)-6 signaling, an active pharmacological target upstream of CRP, is associated with these amyloid-related pathologies remains unknown.

Methods

We used 26 CRP-lowering variants near the IL-6 receptor gene to perform Mendelian randomization analyses for AD (111,326 cases, 677,663 controls) and ICH (1545 cases, 1481 controls). We explored the effect of genetically proxied IL-6 signaling on serum, cerebrospinal fluid (CSF), and brain proteome (971 individuals).

Results

Genetically upregulated IL-6 receptor-mediated signaling was associated with lower risk of AD (OR per increment in se

SUBMITTER: Myserlis EP 

PROVIDER: S-EPMC11349601 | biostudies-literature | 2024 Jul-Sep

REPOSITORIES: biostudies-literature