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

Vogels, Thomas ; Leuzy, Antoine LU ; Cicognola, Claudia ; Ashton, Nicholas J. ; Smolek, Tomas ; Novak, Michal ; Blennow, Kaj LU ; Zetterberg, Henrik LU ; Hromadka, Tomas and Zilka, Norbert , et al. (2019) In Biological Psychiatry
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... (More)

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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Contribution to journal
publication status
epub
subject
keywords
Alzheimer's disease, Cerebrospinal fluid, Models, Positron emission tomography, Spreading, Tau
in
Biological Psychiatry
publisher
Society of Biological Psychiatry Published by Elsevier Inc.
external identifiers
  • scopus:85075333246
  • pmid:31735253
ISSN
0006-3223
DOI
10.1016/j.biopsych.2019.09.019
language
English
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yes
id
d72bfcca-d5d0-4825-ab9a-19cc1c493fc2
date added to LUP
2019-12-11 10:34:37
date last changed
2020-01-13 02:35:45
@article{d72bfcca-d5d0-4825-ab9a-19cc1c493fc2,
  abstract     = {<p>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.</p>},
  author       = {Vogels, Thomas and Leuzy, Antoine and Cicognola, Claudia and Ashton, Nicholas J. and Smolek, Tomas and Novak, Michal and Blennow, Kaj and Zetterberg, Henrik and Hromadka, Tomas and Zilka, Norbert and Schöll, Michael},
  issn         = {0006-3223},
  language     = {eng},
  month        = {10},
  publisher    = {Society of Biological Psychiatry Published by Elsevier Inc.},
  series       = {Biological Psychiatry},
  title        = {Propagation of Tau Pathology : Integrating Insights From Postmortem and In Vivo Studies},
  url          = {http://dx.doi.org/10.1016/j.biopsych.2019.09.019},
  doi          = {10.1016/j.biopsych.2019.09.019},
  year         = {2019},
}