Unknown

Dataset Information

0

Familial Alzheimer's Disease-Related Mutations Differentially Alter Stability of Amyloid-Beta Aggregates.

ABSTRACT: Amyloid-beta (Aβ) deposition as senile plaques is a pathological hallmark of Alzheimer's disease (AD). AD is characterized by a large level of heterogeneity in amyloid pathology, whose molecular origin is poorly understood. Here, we employ NMR spectroscopy and MD simulation at ambient and high pressures and investigate how AD-related mutations in Aβ peptide influence the stability of Aβ aggregates. The pressure-induced monomer dissociation from Aβ aggregates monitored by NMR demonstrated that the Iowa (D23N), Arctic (E22G), and Osaka (ΔE22) mutations altered the pressure stability of Aβ40 aggregates in distinct manners. While the NMR data of monomeric Aβ40 showed only small localized effects of mutations, the MD simulation of mutated Aβ fibrils revealed their distinct susceptibility to elevated pressure. Our data propose a structural basis for the distinct stability of various Aβ fibrils and highlights "stability" as a molecular property potentially contributing to the large heterogeneity of amyloid pathology in AD.

SUBMITTER: Rezaei-Ghaleh N 

PROVIDER: S-EPMC9940190 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Familial Alzheimer's Disease-Related Mutations Differentially Alter Stability of Amyloid-Beta Aggregates.

Rezaei-Ghaleh Nasrollah N   Amininasab Mehriar M   Giller Karin K   Becker Stefan S  

The journal of physical chemistry letters 20230203 6

Amyloid-beta (Aβ) deposition as senile plaques is a pathological hallmark of Alzheimer's disease (AD). AD is characterized by a large level of heterogeneity in amyloid pathology, whose molecular origin is poorly understood. Here, we employ NMR spectroscopy and MD simulation at ambient and high pressures and investigate how AD-related mutations in Aβ peptide influence the stability of Aβ aggregates. The pressure-induced monomer dissociation from Aβ aggregates monitored by NMR demonstrated that th  ...[more]

Similar Datasets

Unknown Familial Alzheimer's disease mutations differentially alter amyloid β-protein oligomerization.
| S-EPMC3503339 | biostudies-literature
Unknown Familial Alzheimer's disease mutations alter the stability of the amyloid beta-protein monomer folding nucleus.
| S-EPMC2034231 | biostudies-other
Unknown Familial Alzheimer's disease mutations in amyloid protein precursor alter proteolysis by γ-secretase to increase amyloid β-peptides of ≥45 residues.
| S-EPMC7948801 | biostudies-literature
Unknown Familial Alzheimer's disease mutations in presenilin 1 do not alter levels of the secreted amyloid-beta protein precursor generated by beta-secretase cleavage.
| S-EPMC3260056 | biostudies-literature
Unknown Magnetoelectric dissociation of Alzheimer's β-amyloid aggregates.
| S-EPMC9094672 | biostudies-literature
Unknown Mutations of beta-amyloid precursor protein alter the consequence of Alzheimer's disease pathogenesis.
| S-EPMC6352587 | biostudies-literature
Unknown The genetic landscape for amyloid beta fibril nucleation accurately discriminates familial Alzheimer's disease mutations.
| S-EPMC7943193 | biostudies-literature
Unknown Soluble Amyloid-beta Aggregates from Human Alzheimer's Disease Brains.
| S-EPMC5137165 | biostudies-literature
Unknown Medin co-aggregates with vascular amyloid-β in Alzheimer's disease.
| S-EPMC9712113 | biostudies-literature
Unknown Seeding, maturation and propagation of amyloid β-peptide aggregates in Alzheimer's disease.
| S-EPMC10234116 | biostudies-literature