Wesenhagen, Kirsten EJ;
Gobom, Johan;
Bos, Isabelle;
Vos, Stephanie JB;
Martinez-Lage, Pablo;
Popp, Julius;
Tsolaki, Magda;
... Tijms, Betty M; + view all
(2022)
Effects of age, amyloid, sex, and APOE ε4 on the CSF proteome in normal cognition.
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
, 14
(1)
, Article e12286. 10.1002/dad2.12286.
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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.
| Type: | Article |
|---|---|
| Title: | Effects of age, amyloid, sex, and APOE ε4 on the CSF proteome in normal cognition |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/dad2.12286 |
| Publisher version: | https://doi.org/10.1002/dad2.12286 |
| Language: | English |
| Additional information: | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Keywords: | Alzheimer's Disease Neuroimaging Initiative |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10150501 |
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