On the lack of polymorphism in Aβ-peptide aggregates derived from patient brains

Protein Science : a Publication of the Protein Society
Erik J AlredUlrich H E Hansmann

Abstract

The amyloid beta (Aβ) oligomers and fibrils that are found in neural tissues of patients suffering from Alzheimer's disease may either cause or contribute to the pathology of the disease. In vitro, these Aβ-aggregates are characterized by structural polymorphism. However, recent solid state NMR data of fibrils acquired post mortem from the brains of two Alzheimer's patients indicate presence of only a single, patient-specific structure. Using enhanced molecular dynamic simulations we investigate the factors that modulate the stability of Aβ-fibrils. We find characteristic differences in molecular flexibility, dynamics of interactions, and structural behavior between the brain-derived Aβ-fibril structure and in vitro models. These differences may help to explain the lack of polymorphism in fibrils collected from patient brains, and have to be taken into account when designing aggregation inhibitors and imaging agents for Alzheimer's disease.

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Citations

Jan 10, 2016·The Journal of Chemical Physics·Manikanthan BhavarajuUlrich H E Hansmann
Sep 29, 2015·The Journal of Physical Chemistry. B·Workalemahu M BerhanuUlrich H E Hansmann
Aug 4, 2015·The Journal of Physical Chemistry. B·Niyati D Parikh, Dmitri K Klimov
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Nov 8, 2018·Biotechnic & Histochemistry : Official Publication of the Biological Stain Commission·Richard W Dapson
Jul 28, 2017·Scientific Reports·Wenhui Xi, Ulrich H E Hansmann
Jul 10, 2021·The Journal of Chemical Physics·S R NateshE J Haddadian

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