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@ARTICLE{Gerresheim:890029,
author = {Gerresheim, Else F. and Herring, Arne and Gremer, Lothar
and Müller‐Schiffmann, Andreas and Keyvani, Kathy and
Korth, Carsten},
title = {{T}he interaction of insoluble {A}myloid‐β with soluble
{A}myloid‐β dimers decreases {A}myloid‐β plaque
numbers},
journal = {Neuropathology $\&$ applied neurobiology},
volume = {47},
number = {5},
issn = {1365-2990},
address = {Oxford [u.a.]},
publisher = {Wiley-Blackwell},
reportid = {FZJ-2021-00623},
pages = {603-610},
year = {2021},
abstract = {ObjectivesThe heterogeneity of Amyloid‐beta (Aβ) plaque
load in patients with Alzheimer's disease (AD) has puzzled
neuropathology. Since brain Aβ plaque load does not
correlate with cognitive decline, neurotoxic soluble Aβ
oligomers have been championed as disease‐causing agents
in early AD. So far, investigating molecular interactions
between soluble oligomeric Aβ and insoluble Aβ in vivo has
been difficult because of the abundance of Aβ oligomer
species and the kinetic equilibrium in which they coexist.
Here, we investigated whether Aβ plaque heterogeneity
relates to interactions of different Aβ
conformers.Materials and MethodsWe took advantage of
transgenic mice that generate exclusively Aβ dimers
(tgDimer mice) but do not develop Aβ plaques or
neuroinflammation during their lifetime, crossed them to the
transgenic CRND8 mice that develop plaques after 90 days and
measured Aβ plaque load using immunohistochemical and
biochemical assays. Furthermore, we performed in vitro
thioflavin T (ThT) aggregation assays titrating synthetic
Aβ42‐S8C dimers into fibril‐forming synthetic
Aβ42.ResultsWe observed a lower number of Aβ plaques in
the brain of double transgenic mice compared to tgCRND8 mice
alone while the average plaque size remained unaltered.
Corroborating these in vivo findings, synthetic Aβ‐S8C
dimers inhibited fibril formation of wild‐type Aβ also in
vitro, seen by an increased half‐time in the ThT
assay.ConclusionsOur study indicates that Aβ dimers
directly interfere with Aβ fibril formation in vivo and in
vitro. The variable interaction of Aβ dimers with insoluble
Aβ seeds could thus contribute to the heterogeneity of Aβ
plaque load in AD patients.},
cin = {IBI-7},
ddc = {610},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5244 - Information Processing in Neuronal Networks
(POF4-524)},
pid = {G:(DE-HGF)POF4-5244},
typ = {PUB:(DE-HGF)16},
pubmed = {33338256},
UT = {WOS:000605339600001},
doi = {10.1111/nan.12685},
url = {https://juser.fz-juelich.de/record/890029},
}