Comprehensive profiling of Aβ40 and Aβ42 fibril-interacting proteins reveals PRKCG as a drug-targetable regulator of amyloidogenesis in Alzheimer's disease.

ABSTRACT:

Introduction

Proteins interacting with amyloid beta (Aβ) fibrils could be key to plaque formation in Alzheimer's disease (AD) and represent potential biomarkers and therapeutic targets. Previous proteomic studies using microdissected plaques might have captured non-specific components rather than true Aβ interactors.

Methods

Biotinylated Aβ40 or Aβ42 peptides were induced to form fibrils, with Scrambled peptides as controls, and incubated with protein extracts from AD and control prefrontal cortex tissue. Pull-down assays coupled with label-free proteomics identified fibril interactors. Dysregulation and localization were assessed by Western blot, immunofluorescence, immunocytochemistry, immunohistochemistry, and in silico analyses.

Results

We identified 185 Aβ40- and

SUBMITTER: Montero-Calle A 

PROVIDER: S-EPMC12828073 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature