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@ARTICLE{RezaeiGhaleh:996736,
author = {Rezaei-Ghaleh, Nasrollah and Amininasab, Mehriar and
Giller, Karin and Becker, Stefan},
title = {{F}amilial {A}lzheimer’s {D}isease-{R}elated {M}utations
{D}ifferentially {A}lter {S}tability of {A}myloid-{B}eta
{A}ggregates},
journal = {The journal of physical chemistry letters},
volume = {14},
issn = {1948-7185},
address = {Washington, DC},
publisher = {ACS},
reportid = {FZJ-2023-01152},
pages = {1427 - 1435},
year = {2023},
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.},
cin = {IBI-7},
ddc = {530},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524)},
pid = {G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)16},
pubmed = {36734539},
UT = {WOS:000928873500001},
doi = {10.1021/acs.jpclett.2c03729},
url = {https://juser.fz-juelich.de/record/996736},
}