Unveiling Proteomic and Peptide-Level Modifications in Cerebrospinal Fluid and Plasma in Normal Cognitive Aging

ABSTRACT: This study presents a comprehensive proteomic and peptide level analysis of matched cerebrospinal fluid (CSF) and plasma samples from cognitively normal young (n=52) and older (n=40) adults, employing mass spectrometry to elucidate protein-level and peptide-level changes associated with normal cognitive aging. Differential abundance analysis revealed significant upregulation of extracellular matrix components (ECM), coagulation, and inflammatory pathways in CSF and downregulation of insulin-like growth factor-1 (IGF-1) signaling pathway in plasma with aging based on gene set enrichment and weighted correlation network analyses. Novel alternative protein cleavage/splicing and phosphorylation patterns were identified in many proteins involved in lipid metabolism, ECM structure, axonogenesis and synaptic activity such as APP, APOE, COL4A2, NRXN1, and NRCAM. The examination of alternative cleavage/splicing and phosphorylation events in CSF and plasma provided unprecedented insights into age-associated protein modifications. These findings offer potential biomarkers and therapeutic targets and highlight the complex molecular landscape of normal cognitive aging.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo

SUBMITTER: Abhay Moghekar   Roland Bruderer  

PROVIDER: MSV000097888 | MassIVE | Wed May 14 04:58:00 BST 2025

SECONDARY ACCESSION(S): PXD063924

REPOSITORIES: MassIVE