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Propagation of Tau Pathology: Integrating Insights From Postmortem and In Vivo Studies.

Journal article
Authors Thomas Vogels
Antoine Leuzy
Claudia Cicognola
Nicholas J. Ashton
Tomas Smolek
Michal Novak
Kaj Blennow
Henrik Zetterberg
Tomas Hromadka
Norbert Zilka
Michael Schöll
Published in Biological psychiatry
Volume 87
Pages 808–818
ISSN 1873-2402
Publication year 2020
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Wallenberg Centre for Molecular and Translational Medicine
Pages 808–818
Language en
Links dx.doi.org/10.1016/j.biopsych.2019....
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Neurochemistry

Abstract

Cellular accumulation of aggregated forms of the protein tau is a defining feature of so-called tauopathies such as Alzheimer's disease, progressive supranuclear palsy, and chronic traumatic encephalopathy. A growing body of literature suggests that conformational characteristics of tau filaments, along with regional vulnerability to tau pathology, account for the distinct histopathological morphologies, biochemical composition, and affected cell types seen across these disorders. In this review, we describe and discuss recent evidence from human postmortem and clinical biomarker studies addressing the differential vulnerability of brain areas to tau pathology, its cell-to-cell transmission, and characteristics of the different strains that tau aggregates can adopt. Cellular biosensor assays are increasingly used in human tissue to detect the earliest forms of tau pathology, before overt histopathological lesions (i.e., neurofibrillary tangles) are apparent. Animal models with localized tau expression are used to uncover the mechanisms that influence spreading of tau aggregates. Further, studies of human postmortem-derived tau filaments from different tauopathies injected in rodents have led to striking findings that recapitulate neuropathology-based staging of tau. Furthermore, the recent advent of tau positron emission tomography and novel fluid-based biomarkers render it possible to study the temporal progression of tau pathology in vivo. Ultimately, evidence from these approaches must be integrated to better understand the onset and progression of tau pathology across tauopathies. This will lead to improved methods for the detection and monitoring of disease progression and, hopefully, to the development and refinement of tau-based therapeutics.

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