From Soluble A β to Progressive A β Aggregation: Could Prion‐Like Templated Misfolding Play a Role?
Year: 2013
Type: review
Abstract: Accumulation, aggregation and deposition of Aβ peptides are pathological hallmarks in the brains of individuals affected by Alzheimer's disease (AD) or by cerebral β-amyloid angiopathy (Aβ-CAA). While Aβ is a peptide of yet largely unknown function, it is constantly produced in the human brain where it normally remains in a soluble state. However, Aβ peptides are aggregation prone by their intrinsic ability to adopt alternative conformations rich in β-sheet structure that aggregate into oligomeric as well as fibrillar formations. This transition from soluble to aggregated state has been hypothesized to initiate the pathological cascade and is therefore subject to intensive research. Mounting evidence suggests prion-like templated misfolding as the biochemical phenomenon responsible for promoting progressive Aβ aggregation. Here, we review studies in vitro and in vivo that suggest that cerebral Aβ aggregation may indeed progress via prion-like templated misfolding. The implications of these findings are discussed with respect to understanding initiation and progression of the disease and to developing therapeutics.
Source: Brain Pathology
DOI: 10.1111/bpa.12049
Author: Yvonne S. Eisele
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1532832054