Pyroglutamation of amyloid-βx-42 (Aβx-42) followed by Aβ1-40 deposition underlies plaque polymorphism in progressing Alzheimer's disease pathology.

ABSTRACT: Amyloid-β (Aβ) pathology in Alzheimer's disease (AD) is characterized by the formation of polymorphic deposits comprising diffuse and cored plaques. Because diffuse plaques are predominantly observed in cognitively unaffected, amyloid-positive (CU-AP) individuals, pathogenic conversion into cored plaques appears to be critical to AD pathogenesis. Herein, we identified the distinct Aβ species associated with amyloid polymorphism in brain tissue from individuals with sporadic AD (s-AD) and CU-AP. To this end, we interrogated Aβ polymorphism with amyloid conformation-sensitive dyes and a novel in situ MS paradigm for chemical characterization of hyperspectrally delineated plaque morphotypes. We found that maturation of diffuse into cored plaques correlated with increased Aβ1-40 deposit

SUBMITTER: Michno W 

PROVIDER: S-EPMC6497931 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature