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.
[doi:10.25345/C5ZC7S677]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: cerebrospinal fluid, plasma, normal cognitive aging, DIA mass spectrometry, data-independent acquisition, deep proteomics, peptide-level analysis, alternative cleavage, alternative splicing ; DatasetType:Proteomics
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Principal Investigators: (in alphabetical order) |
Abhay Moghekar, Johns Hopkins University, USA Roland Bruderer, Biognosys AG, Switzerland |
| Submitting User: | roland_bruderer |
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