Synaptic proteins associated with cognitive performance and neuropathology in older humans revealed by multiplexed fractionated proteomics

• DOI: 10.1016/j.neurobiolaging.2021.04.012
• Publication Date: 2021-04-24T06:01:27Z
• Authors: Becky C. Carlyle; Savannah E. Kandi...; Johannes Kreuzer; Sudeshna Das; Bianca A. Trombetta; Yikai Kuo; David A. Bennett; Julie A. Schneider; Vladislav A. Petyuk; Robert R. Kitchen; Robert Morris; Angus C. Nairn; Bradley T. Hyman; Wilhelm Haas; Steven E. Arnold
• Keywords: Neuropathology; Cognitive Decline

Alzheimer's disease (AD) is defined by the presence of abundant amyloid-β (Aβ) and tau neuropathology. While this neuropathology necessary for AD diagnosis, it not sufficient causing cognitive impairment. Up to one third community dwelling older adults harbor intermediate high levels at death yet demonstrate no significant Conversely, there are individuals who exhibit dementia with gross explanatory In prior studies, synapse loss correlated To understand how synaptic composition changes in relation cognition, multiplexed liquid chromatography mass-spectrometry was used quantify enriched proteins from parietal association cortex 100 subjects contrasting pathology performance. 123 unique were significantly associated diagnostic category. Functional analysis showed enrichment serotonin release oxidative phosphorylation categories normal (cognitively unimpaired, low neuropathology) "resilient" (unimpaired despite pathology) individuals. contrast, frail individuals, (low pathology, impaired cognition) a metabolic shift towards glycolysis increased proteasome subunits.