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

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

Author information

1
Department of Neurology, Clinical Dementia Center and DZNE, Georg-August University, University Medical Center Göttingen (UMG), Göttingen, Germany.
2
Institute of Neuropathology, IDIBELL-University Hospital Bellvitge, University of Barcelona, Hospitalet de Llobregat, Spain.
3
CIBERNED (Network center for biomedical research of neurodegenerative diseases), Institute Carlos III, Ministry of Health, Spain.

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

PMID:
28671123
DOI:
10.3233/JAD-170237
[Indexed for MEDLINE]

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