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

Olamide Abiose, Jarod Rutledge, Patricia Moran-Losada, 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

Research output: Contribution to journalArticlepeer-review

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) proteins quantified by SomaLogic, Inc., in a cohort of participants along the AD clinical spectrum. We then replicated this network in an independent cohort of CU older adults and related these modules to clinically-relevant outcomes. RESULTS: We discovered modules enriched for phosphorylation and ubiquitination that were associated with abnormal amyloid status, as well as p-tau181 (M4: β = 2.44, p < 0.001, M7: β = 2.57, p < 0.001) and executive function performance (M4: β = −2.00, p = 0.005, M7: β = −2.39, p < 0.001). DISCUSSION: In leveraging CSF proteomic data from individuals spanning the clinical spectrum of AD, we highlight the importance of post-translational modifications for early cognitive and pathological changes.

Original languageEnglish
Pages (from-to)1851-1867
Number of pages17
JournalAlzheimer's and Dementia
Volume20
Issue number3
DOIs
StateAccepted/In press - 2023

Keywords

  • aging
  • Alzheimer's disease
  • autophagy
  • cerebral spinal fluid
  • clinically unimpaired
  • protein co-expression network
  • ubiquitination

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