Amyloid fibril proteomics of AD brains reveals modifiers of aggregation and toxicity.

ABSTRACT:

Background

The accumulation of amyloid beta (Aβ) peptides in fibrils is prerequisite for Alzheimer's disease (AD). Our understanding of the proteins that promote Aβ fibril formation and mediate neurotoxicity has been limited due to technical challenges in isolating pure amyloid fibrils from brain extracts.

Methods

To investigate how amyloid fibrils form and cause neurotoxicity in AD brain, we developed a robust biochemical strategy. We benchmarked the success of our purifications using electron microscopy, amyloid dyes, and a large panel of Aβ immunoassays. Tandem mass-spectrometry based proteomic analysis workflows provided quantitative measures of the amyloid fibril proteome. These methods allowed us to compare amyloid fibril composition from human AD brains, three amyloid

SUBMITTER: Upadhyay A 

PROVIDER: S-EPMC10503190 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature