期刊
BRAIN PATHOLOGY
卷 31, 期 5, 页码 -出版社
WILEY
DOI: 10.1111/bpa.12941
关键词
amyloid plaque; A beta oligomer; human brain; neuropathology; PrPC
资金
- Japan Agency for Medical Research and Development [19mk0101104j0702]
- JSPS [17K08524, 17K08705]
- Grants-in-Aid for Scientific Research [17K08524, 17K08705] Funding Source: KAKEN
The interactions between Aβ oligomers and PrPC may play a crucial role in the development of Alzheimer's disease, especially in the human brain. The accumulation of PrPC plaques is associated with more soluble Aβ oligomers and may appear even before the disease onset.
Alzheimer's disease (AD) is the main cause of dementia, and beta-amyloid (A beta) is a central factor in the initiation and progression of the disease. Different forms of AB have been identified as monomers, oligomers, and amyloid fibrils. Many proteins have been implicated as putative receptors of respective forms of All Distinct forms of A beta 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 AD oligomers. The interaction of A beta oligomers with PrPC is important to synaptic dysfunction and loss. The binding of A beta 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 A beta oligomers and PrPC remain unclear, especially in the human brain. We immunohistochemically investigated the relationship between A beta 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 A beta oligomers without stacked beta-sheet fibril structures. Our results suggest that PrPC accumulating plaques are associated with more soluble A beta oligomers, and appear even prior to AD. The investigation of PrPC accumulating plaques may provide new insights into AD.
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