Prion Protein Interactome: Identifying Novel Targets in Slowly and Rapidly Progressive Forms of Alzheimer's Disease

J Alzheimers Dis. 2017;59(1):265-275. doi: 10.3233/JAD-170237.

Abstract

Rapidly progressive Alzheimer's disease (rpAD) is a variant of AD distinguished by a rapid decline in cognition and short disease duration from onset to death. While attempts to identify rpAD based on biomarker profile classifications have been initiated, the mechanisms which contribute to the rapid decline and prion mimicking heterogeneity in clinical signs are still largely unknown. In this study, we characterized prion protein (PrP) expression, localization, and interactome in rpAD, slow progressive AD, and in non-dementia controls. PrP along with its interacting proteins were affinity purified with magnetic Dynabeads Protein-G, and were identified using Q-TOF-ESI/MS analysis. Our data demonstrated a significant 1.2-fold decrease in di-glycosylated PrP isoforms specifically in rpAD patients. Fifteen proteins appeared to interact with PrP and only two proteins3/4histone H2B-type1-B and zinc alpha-2 protein3/4were specifically bound with PrP isoform isolated from rpAD cases. Our data suggest distinct PrP involvement in association with the altered PrP interacting protein in rpAD, though the pathophysiological significance of these interactions remains to be established.

Keywords: Aldolase A; Alzheimer’s disease; co-immunofluorescence; co-immunoprecipitation; histone; myelin P2; peroxiredoxin 1; prion; proteomics; synapsin; tubulin; zinc.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / complications
  • Alzheimer Disease / pathology*
  • Brain / metabolism*
  • Carrier Proteins / metabolism
  • Cognition Disorders / etiology
  • Cognition Disorders / pathology*
  • Creutzfeldt-Jakob Syndrome / complications
  • Creutzfeldt-Jakob Syndrome / pathology*
  • Disease Progression*
  • Female
  • Glycoproteins / metabolism
  • Histones / metabolism
  • Humans
  • Male
  • Middle Aged
  • Prion Proteins / metabolism*

Substances

  • AZGP1 protein, human
  • Carrier Proteins
  • Glycoproteins
  • Histones
  • Prion Proteins
  • histone H2B type 1-A