Dataset Information

Effects of age, amyloid, sex, and APOE ε4 on the CSF proteome in normal cognition.

ABSTRACT:

Introduction

It is important to understand which biological processes change with aging, and how such changes are associated with increased Alzheimer's disease (AD) risk. We studied how cerebrospinal fluid (CSF) proteomics changed with age and tested if associations depended on amyloid status, sex, and apolipoprotein E Ɛ4 genotype.

Methods

We included 277 cognitively intact individuals aged 46 to 89 years from Alzheimer's Disease Neuroimaging Initiative, European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery, and Metabolic Syndrome in Men. In total, 1149 proteins were measured with liquid chromatography mass spectrometry with multiple reaction monitoring/Rules-Based Medicine, tandem mass tag mass spectrometry, and SOMAscan. We tested associations between age and protein levels in linear models and tested enrichment for Reactome pathways.

Results

Levels of 252 proteins increased with age independently of amyloid status. These proteins were associated with immune and signaling processes. Levels of 21 proteins decreased with older age exclusively in amyloid abnormal participants and these were enriched for extracellular matrix organization.

Discussion

We found amyloid-independent and -dependent CSF proteome changes with older age, perhaps representing physiological aging and early AD pathology.

SUBMITTER: Wesenhagen KEJ

PROVIDER: S-EPMC9074716 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Effects of age, amyloid, sex, and <i>APOE</i> ε4 on the CSF proteome in normal cognition.

Wesenhagen Kirsten E J KEJ Gobom Johan J Bos Isabelle I Vos Stephanie J B SJB Martinez-Lage Pablo P Popp Julius J Tsolaki Magda M Vandenberghe Rik R Freund-Levi Yvonne Y Verhey Frans F Lovestone Simon S Streffer Johannes J Dobricic Valerija V Bertram Lars L Blennow Kaj K Pikkarainen Maria M Hallikainen Merja M Kuusisto Johanna J Laakso Markku M Soininen Hilkka H Scheltens Philip P Zetterberg Henrik H Teunissen Charlotte E CE Visser Pieter Jelle PJ Tijms Betty M BM

Alzheimer's & dementia (Amsterdam, Netherlands) 20220506 1

<h4>Introduction</h4>It is important to understand which biological processes change with aging, and how such changes are associated with increased Alzheimer's disease (AD) risk. We studied how cerebrospinal fluid (CSF) proteomics changed with age and tested if associations depended on amyloid status, sex, and apolipoprotein E Ɛ4 genotype.<h4>Methods</h4>We included 277 cognitively intact individuals aged 46 to 89 years from Alzheimer's Disease Neuroimaging Initiative, European Medical Informati ...[more]

PMID: 35571963

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