Chronic cerebral hypoperfusion shifts the equilibrium of amyloid β oligomers to aggregation-prone species with higher molecular weight

Scientific Reports
Taro BannaiAtsushi Iwata

Abstract

Epidemiological studies have shown that atherosclerotic risk factors accelerate the pathological process underlying Alzheimer's disease (AD) via chronic cerebral hypoperfusion. In this study, we aimed to clarify the mechanisms by which cerebral hypoperfusion may exacerbate AD pathology. We applied bilateral common carotid artery stenosis (BCAS) to a mice model of AD and evaluated how the equilibrium of amyloid β oligomers respond to hypoperfusion. BCAS accelerated amyloid β (Aβ) convergence to the aggregation seed, facilitating the growth of Aβ plaques, but without changing the total Aβ amount in the brain. Furthermore, Aβ oligomers with high molecular weight increased in the brain of BCAS-operated mice. Considering Aβ is in an equilibrium among monomeric, oligomeric, and aggregation forms, our data suggest that cerebral hypoperfusion after BCAS shifted this equilibrium to a state where a greater number of Aβ molecules participate in Aβ assemblies to form aggregation-prone Aβ oligomers with high molecular weight. The reduced blood flow in the cerebral arteries due to BCAS attenuated the dynamics of the interstitial fluid leading to congestion, which may have facilitated Aβ aggregation. We suggest that cerebral hypoperfusion may...Continue Reading

References

Dec 22, 1999·Neurology·A OttM M Breteler
May 5, 2001·Biomolecular Engineering·J L JankowskyD R Borchelt
Jul 10, 2003·Lancet Neurology·Gustavo C RománHelena C Chui
Oct 9, 2004·Stroke; a Journal of Cerebral Circulation·Masunari ShibataHidekazu Tomimoto
Feb 26, 2010·Journal of Alzheimer's Disease : JAD·Leon Flicker
Jan 20, 2011·Journal of Neurochemistry·Kenjiro Ono, Masahito Yamada
Feb 26, 2011·The Journal of Biological Chemistry·Suman NagSudipta Maiti
Nov 4, 2011·Nature Reviews. Neuroscience·Berislav V Zlokovic
Jan 31, 2012·Nature Neuroscience·Iryna BenilovaBart De Strooper
May 4, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shuko TakedaBradley T Hyman
Jun 5, 2013·Stroke; a Journal of Cerebral Circulation·Jeffrey J Iliff, Maiken Nedergaard
Aug 14, 2013·Nature Reviews. Neurology·Raj N Kalaria, Masafumi Ihara
Dec 20, 2014·Current Alzheimer Research·Robert J BaranelloKumar Sambamurti
Feb 18, 2015·Nature Reviews. Neurology·Niels D Prins, Philip Scheltens
Jul 22, 2015·Nature Reviews. Neurology·Jenna M Tarasoff-ConwayMony J de Leon
Feb 24, 2016·Journal of the American Heart Association·Yorito HattoriMasafumi Ihara
Aug 22, 2017·Translational Neurodegeneration·Xue-Mei Qi, Jian-Fang Ma
Oct 19, 2017·Proceedings of the National Academy of Sciences of the United States of America·Tatsuo ManoAtsushi Iwata

❮ Previous
Next ❯

Citations

Dec 11, 2019·International Journal of Molecular Sciences·Kazuo WashidaMasafumi Ihara
Aug 29, 2019·Frontiers in Computational Neuroscience·Leon StefanovskiUNKNOWN Alzheimer's Disease Neuroimaging Initiative
Jul 1, 2020·Journal of Alzheimer's Disease : JAD·Ernesto SolisErin R Hascup
Jul 16, 2019·Journal of Alzheimer's Disease : JAD·Rebecca Parodi-RullánSilvia Fossati
Jun 25, 2020·Current Cardiology Reports·Gianlorenzo DanieleFederica Del Monte
Feb 26, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Sanny SchefferMat J A P Daemen
Aug 14, 2021·Scientific Reports·João PinhoAna Sofia Costa
Mar 19, 2021·Alzheimer Disease and Associated Disorders·Carolyn S KaufmanSandra A Billinger

❮ Previous
Next ❯

Methods Mentioned

BETA
size exclusion chromatography
ELISA
transgenic
dissection

Key Resources (RRID) Mentioned

AB_2289606
AB_1310605
AB_444310
AB_298849
AB_2149572
AB_11130255
AB_303947
AB_2234877
AB_10585132
AB_10149308

Software Mentioned

GraphPad Prism
ImageJ

Related Concepts

Related Feeds

Carotid Artery Diseases

Carotid artery disease is a group of pathological conditions of the carotid artery. Discover the latest research on carotid artery disease here.