Vogels, T;
Leuzy, A;
Cicognola, C;
Ashton, NJ;
Smolek, T;
Novak, M;
Blennow, K;
... Schöll, M; + view all
(2019)
Propagation of Tau Pathology: Integrating Insights From Postmortem and In Vivo Studies.
Biological Psychiatry
10.1016/j.biopsych.2019.09.019.
(In press).
Preview |
Text
1-s2.0-S0006322319317445-main.pdf - Published Version Download (1MB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | Propagation of Tau Pathology: Integrating Insights From Postmortem and In Vivo Studies |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.biopsych.2019.09.019 |
| Publisher version: | https://doi.org/10.1016/j.biopsych.2019.09.019 |
| Language: | English |
| Additional information: | Copyright © 2019 Society of Biological Psychiatry. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | Alzheimer’s disease, Cerebrospinal fluid, Models, Positron emission tomography, Spreading, Tau |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10087106 |
Archive Staff Only
 |
View Item |
