Open AccessFrom Soluble A β to Progressive A β Aggregation: Could Prion‐Like Templated Misfolding Play a Role?
Author(s) -
Eisele Yvonne S.
Publication year - 2013
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12049
Subject(s) - cerebral amyloid angiopathy , protein aggregation , in vitro , in vivo , protein folding , amyloid (mycology) , chemistry , peptide , fibril , function (biology) , microbiology and biotechnology , prion protein , proteostasis , neuroscience , disease , biophysics , biology , biochemistry , medicine , dementia , pathology , genetics , inorganic chemistry
Accumulation, aggregation and deposition of A β peptides are pathological hallmarks in the brains of individuals affected by A lzheimer's disease ( AD ) or by cerebral β‐amyloid angiopathy ( A β‐ CAA ). While A β 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, A β 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 A β aggregation. Here, we review studies in vitro and in vivo that suggest that cerebral A β 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.