Neuroscience Insights (Oct 2023)

Unveiling Resilience to Alzheimer’s Disease: Insights From Brain Regional Proteomic Markers

  • Zhi Huang,
  • Gennifer E Merrihew,
  • Eric B Larson,
  • Jea Park,
  • Deanna Plubell,
  • Edward J Fox,
  • Kathleen S Montine,
  • C Dirk Keene,
  • Caitlin S Latimer,
  • James Y Zou,
  • Michael J MacCoss,
  • Thomas J Montine

DOI
https://doi.org/10.1177/26331055231201600
Journal volume & issue
Vol. 18

Abstract

Read online

Studying proteomics data of the human brain could offer numerous insights into unraveling the signature of resilience to Alzheimer’s disease. In our previous study with rigorous cohort selection criteria that excluded 4 common comorbidities, we harnessed multiple brain regions from 43 research participants with 12 of them displaying cognitive resilience to Alzheimer’s disease. Based on the previous findings, this work focuses on 6 proteins out of the 33 differentially expressed proteins associated with resilience to Alzheimer’s disease. These proteins are used to construct a decision tree classifier, enabling the differentiation of 3 groups: (i) healthy control, (ii) resilience to Alzheimer’s disease, and (iii) Alzheimer’s disease with dementia. Our analysis unveiled 2 important regional proteomic markers: Aβ peptides in the hippocampus and PA1B3 in the inferior parietal lobule. These findings underscore the potential of using distinct regional proteomic markers as signatures in characterizing the resilience to Alzheimer’s disease.