Post‐translational modifications linked to preclinical Alzheimer's disease–related pathological and cognitive changes

• DOI: 10.1002/alz.13576
• Publication Date: 2023-12-26T05:24:10Z
• Authors: Olamide Abiose; Jarod Rutledge; Patricia Moran‐Lo...; Michael E. Belloy; Edward N. Wilson; Zihuai He; Alexandra N. Trelle; Divya Channappa; America Romero; Jennifer Park; Maya V. Yutsis; Sharon J. Sha; Katrin I. Andreasson; Kathleen L. Poston; Victor W. Henderson; Anthony D. Wagner; Tony Wyss‐Coray; Elizabeth C. Mormino
• Keywords: Proteomics; 0301 basic medicine; Amyloid beta-Peptides; tau Proteins; 03 medical and health sciences; Cognition; Alzheimer Disease; Humans; Cognitive Dysfunction; Protein Processing, Post-Translational; Research Articles; Biomarkers; Aged

Abstract INTRODUCTION In this study, we leverage proteomic techniques to identify communities of proteins underlying Alzheimer's disease (AD) risk among clinically unimpaired (CU) older adults. METHODS We constructed a protein co‐expression network using 3869 cerebrospinal fluid (CSF) quantified by SomaLogic, Inc., in cohort participants along the AD clinical spectrum. then replicated an independent CU adults and related these modules clinically‐relevant outcomes. RESULTS discovered enriched for phosphorylation ubiquitination that were associated with abnormal amyloid status, as well p‐tau 181 (M4: β = 2.44, p < 0.001, M7: 2.57, 0.001) executive function performance −2.00, 0.005, −2.39, 0.001). DISCUSSION leveraging CSF data from individuals spanning spectrum AD, highlight importance post‐translational modifications early cognitive pathological changes.