Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy

Acta Neuropathologica Communications
Yingjian YouCristian A Lasagna-Reeves

Abstract

Cerebral amyloid angiopathy (CAA) is typified by the cerebrovascular deposition of amyloid. Currently, there is no clear understanding of the mechanisms underlying the contribution of CAA to neurodegeneration. Despite the fact that CAA is highly associated with accumulation of Aβ, other types of amyloids have been shown to associate with the vasculature. Interestingly, in many cases, vascular amyloidosis is accompanied by significant tau pathology. However, the contribution of tau to neurodegeneration associated to CAA remains to be determined. We used a mouse model of Familial Danish Dementia (FDD), a neurodegenerative disease characterized by the accumulation of Danish amyloid (ADan) in the vasculature, to characterize the contribution of tau to neurodegeneration associated to CAA. We performed histological and biochemical assays to establish tau modifications associated with CAA in conjunction with cell-based and electrophysiological assays to determine the role of tau in the synaptic dysfunction associated with ADan. We demonstrated that ADan aggregates induced hyperphosphorylation and misfolding of tau. Moreover, in a mouse model for CAA, we observed tau oligomers closely associated to astrocytes in the vicinity of vascula...Continue Reading

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Citations

Mar 12, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Erin L AbnerEdward J Goetzl
May 18, 2020·International Journal of Molecular Sciences·Laura GattiAnna Bersano
Dec 19, 2019·International Journal of Molecular Sciences·Pablo CisternasCristian A Lasagna-Reeves
Jan 28, 2020·Journal of Alzheimer's Disease : JAD·Michael Malek-AhmadiElliott J Mufson
Jan 26, 2021·Frontiers in Neurology·Elisa Canepa, Silvia Fossati
Jul 31, 2019·Free Radical Biology & Medicine·Yiming ChengJames Haorah
Jan 20, 2022·Acta Neuropathologica·Alifiya KapasiJ A Schneider

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Methods Mentioned

BETA
transfection
PCR

Software Mentioned

Coloc
NIS Element Advanced Research
Prism
Clampex
QuantStudio
GraphPad Prism
Fiji
Leica
LAS X

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