Accumulation of cellular prion protein within β-amyloid oligomer plaques in aged human brains

Research output: Contribution to journalArticle

Abstract

Alzheimer's disease (AD) is the main cause of dementia, and β-amyloid (Aβ) is a central factor in the initiation and progression of the disease. Different forms of Aβ have been identified as monomers, oligomers, and amyloid fibrils. Many proteins have been implicated as putative receptors of respective forms of Aβ. Distinct forms of Aβ oligomers are considered to be neurotoxic species that trigger the pathophysiology of AD. It was reported that cellular prion protein (PrPC ) is one of the most selective and high-affinity binding partners of Aβ oligomers. The interaction of Aβ oligomers with PrPC is important to synaptic dysfunction and loss. The binding of Aβ oligomers to PrPC has mostly been studied with synthetic peptides, cell culture, and murine models of AD by biochemical and biological methods. However, the molecular mechanisms underlying the relationship between Aβ oligomers and PrPC remain unclear, especially in the human brain. We immunohistochemically investigated the relationship between Aβ oligomers and PrPC in human brain tissue with and without amyloid pathology. We histologically demonstrate that PrPC accumulates with aging in human brain tissue even prior to AD mainly within diffuse-type amyloid plaques, which are composed of more soluble Aβ oligomers without stacked β-sheet fibril structures. Our results suggest that PrPC accumulating plaques are associated with more soluble Aβ oligomers, and appear even prior to AD. The investigation of PrPC accumulating plaques may provide new insights into AD.

Details

Authors
  • Reisuke H Takahashi
  • Mayumi Yokotsuka
  • Minoru Tobiume
  • Yuko Sato
  • Hideki Hasegawa
  • Toshitaka Nagao
  • Gunnar K Gouras
Organisations
External organisations
  • National Institute of Infectious Diseases, Japan
  • University of Tokyo
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences
Original languageEnglish
Pages (from-to)e12941
JournalBrain Pathology
Publication statusE-pub ahead of print - 2021 Feb 23
Publication categoryResearch
Peer-reviewedYes