Open AccessEffects of age, amyloid, sex, and APOE ε4 on the CSF proteome in normal cognition
Author(s) -
Wesenhagen Kirsten E.J.,
Gobom Johan,
Bos Isabelle,
Vos Stephanie J.B.,
MartinezLage Pablo,
Popp Julius,
Tsolaki Magda,
Vandenberghe Rik,
FreundLevi Yvonne,
Verhey Frans,
Lovestone Simon,
Streffer Johannes,
Dobricic Valerija,
Bertram Lars,
Blennow Kaj,
Pikkarainen Maria,
Hallikainen Merja,
Kuusisto Johanna,
Laakso Markku,
Soininen Hilkka,
Scheltens Philip,
Zetterberg Henrik,
Teunissen Charlotte E.,
Visser Pieter Jelle,
Tijms Betty M.
Publication year - 2022
Publication title -
alzheimer's and dementia: diagnosis, assessment and disease monitoring
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.497
H-Index - 37
ISSN - 2352-8729
DOI - 10.1002/dad2.12286
Subject(s) - apolipoprotein e , proteome , biomarker , disease , proteomics , amyloid (mycology) , cerebrospinal fluid , tandem mass tag , biomarker discovery , alzheimer's disease neuroimaging initiative , alzheimer's disease , apolipoprotein b , medicine , psychology , bioinformatics , biology , pathology , quantitative proteomics , biochemistry , gene , cholesterol
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.