APOE4 Copy Number-Dependent Proteomic Changes in the Cerebrospinal Fluid.

ABSTRACT:

Background

APOE4 has been hypothesized to increase Alzheimer's disease risk by increasing neuroinflammation, though the specific neuroinflammatory pathways involved are unclear.

Objective

Characterize cerebrospinal fluid (CSF) proteomic changes related to APOE4 copy number.

Methods

We analyzed targeted proteomic data from ADNI CSF samples using a linear regression model adjusting for age, sex, and APOE4 copy number, and additional linear models also adjusting for AD clinical status or for CSF A?, tau, or p-tau levels. False discovery rate was used to correct for multiple comparisons correction.

Results

Increasing APOE4 copy number was associated with a significant decrease in a CRP peptide level across all five models (q?ConclusionIncreasing APOE4 copy number was associated with decreased CSF CRP levels across all models, and increased CSF ALDOA, CH3L1, and FABH levels when controlling for CSF A? levels. Increased APOE4 copy number may also be associated with decreased CSF complement pathway protein levels, a hypothesis for investigation in future studies.

SUBMITTER: Berger M 

PROVIDER: S-EPMC7902966 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature