Autocatalytic amplification of Alzheimer-associated Aß42 peptide aggregation in human cerebrospinal fluid.
Commun Biol
; 2: 365, 2019.
Article
in En
| MEDLINE
| ID: mdl-31602414
ABSTRACT
Alzheimer's disease is linked to amyloid ß (Aß) peptide aggregation in the brain, and a detailed understanding of the molecular mechanism of Aß aggregation may lead to improved diagnostics and therapeutics. While previous studies have been performed in pure buffer, we approach the mechanism in vivo using cerebrospinal fluid (CSF). We investigated the aggregation mechanism of Aß42 in human CSF through kinetic experiments at several Aß42 monomer concentrations (0.8-10 µM). The data were subjected to global kinetic analysis and found consistent with an aggregation mechanism involving secondary nucleation of monomers on the fibril surface. A mechanism only including primary nucleation was ruled out. We find that the aggregation process is composed of the same microscopic steps in CSF as in pure buffer, but the rate constant of secondary nucleation is decreased. Most importantly, the autocatalytic amplification of aggregate number through catalysis on the fibril surface is prevalent also in CSF.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptide Fragments
/
Amyloid beta-Peptides
/
Protein Aggregation, Pathological
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Commun Biol
Year:
2019
Document type:
Article
Affiliation country:
Sweden