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Glial cells and adaptive immunity in frontotemporal dementia with tau pathology

Glial cells and adaptive immunity in frontotemporal dementia with tau pathology
Glial cells and adaptive immunity in frontotemporal dementia with tau pathology
Neuroinflammation is involved in the aetiology of many neurodegenerative disorders including Alzheimer’s Disease, Parkinson’s Disease and Motor Neuron Disease. Whether neuroinflammation also plays an important role in the pathophysiology of frontotemporal dementia is less well known. Frontotemportal dementia is a heterogeneous classification which covers many subtypes, with the main pathology known as frontotemporal lobar degeneration. The disease can be categorised with respect to the identity of the protein that causes the frontotemporal lobar degeneration in the brain. The most common subgroup describes diseases caused by frontotemporal lobar degeneration associated with tau aggregation, also known as primary tauopathies. Evidence suggests that neuroinflammation may play a role in primary tauopathies with genome-wide association studies finding enrichment of genetic variants associated with specific inflammation-related gene loci. These loci are related to both the innate immune system, including brain resident microglia, and the adaptive immune system through possible peripheral T cell involvement. This review discusses the genetic evidence and relates it to findings in animal models expressing pathogenic tau as well as to post-mortem and positron emission tomography studies in human disease. Across experimental paradigms, there appears to be a consensus regarding the involvement of innate immunity in primary tauopathies, with increased microglia and astrocyte density and/or activation, as well as increases in pro-inflammatory markers. Whilst it is less clear as to whether inflammation precedes tau aggregation or vice-versa; there is strong evidence to support a microglial contribution to the propagation of hyperphosphorylated in tau frontotemporal lobar degeneration associated with tau aggregation. Experimental evidence - albeit limited – also corroborates genetic data pointing to the involvement of cellular adaptive immunity in primary tauopathies. However, it is still unclear whether brain recruitment of peripheral immune cells is an aberrant result of pathological changes or a physiological aspect of the neuroinflammatory response to the tau pathology.
0006-8950
Hartnell, Iain
46e8c0a1-f5cc-42f9-bc01-911e2dbf4cce
Blum, David
f201306e-d9af-4d7d-bc05-cb463be5f941
Nicoll, James
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Dorothee, Guillaume
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Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Hartnell, Iain
46e8c0a1-f5cc-42f9-bc01-911e2dbf4cce
Blum, David
f201306e-d9af-4d7d-bc05-cb463be5f941
Nicoll, James
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Dorothee, Guillaume
9e91ddc6-d218-4890-9803-abe3d91ffe19
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61

Hartnell, Iain, Blum, David, Nicoll, James, Dorothee, Guillaume and Boche, Delphine (2020) Glial cells and adaptive immunity in frontotemporal dementia with tau pathology. Brain. (In Press)

Record type: Review

Abstract

Neuroinflammation is involved in the aetiology of many neurodegenerative disorders including Alzheimer’s Disease, Parkinson’s Disease and Motor Neuron Disease. Whether neuroinflammation also plays an important role in the pathophysiology of frontotemporal dementia is less well known. Frontotemportal dementia is a heterogeneous classification which covers many subtypes, with the main pathology known as frontotemporal lobar degeneration. The disease can be categorised with respect to the identity of the protein that causes the frontotemporal lobar degeneration in the brain. The most common subgroup describes diseases caused by frontotemporal lobar degeneration associated with tau aggregation, also known as primary tauopathies. Evidence suggests that neuroinflammation may play a role in primary tauopathies with genome-wide association studies finding enrichment of genetic variants associated with specific inflammation-related gene loci. These loci are related to both the innate immune system, including brain resident microglia, and the adaptive immune system through possible peripheral T cell involvement. This review discusses the genetic evidence and relates it to findings in animal models expressing pathogenic tau as well as to post-mortem and positron emission tomography studies in human disease. Across experimental paradigms, there appears to be a consensus regarding the involvement of innate immunity in primary tauopathies, with increased microglia and astrocyte density and/or activation, as well as increases in pro-inflammatory markers. Whilst it is less clear as to whether inflammation precedes tau aggregation or vice-versa; there is strong evidence to support a microglial contribution to the propagation of hyperphosphorylated in tau frontotemporal lobar degeneration associated with tau aggregation. Experimental evidence - albeit limited – also corroborates genetic data pointing to the involvement of cellular adaptive immunity in primary tauopathies. However, it is still unclear whether brain recruitment of peripheral immune cells is an aberrant result of pathological changes or a physiological aspect of the neuroinflammatory response to the tau pathology.

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Glial cells and adaptive immunity - Accepted Manuscript
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Accepted/In Press date: 17 October 2020

Identifiers

Local EPrints ID: 444898
URI: http://eprints.soton.ac.uk/id/eprint/444898
ISSN: 0006-8950
PURE UUID: 6d9fa4a0-110c-4405-84a6-6d246f038099
ORCID for James Nicoll: ORCID iD orcid.org/0000-0002-9444-7246
ORCID for Delphine Boche: ORCID iD orcid.org/0000-0002-5884-130X

Catalogue record

Date deposited: 10 Nov 2020 17:31
Last modified: 17 Oct 2021 04:01

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Contributors

Author: Iain Hartnell
Author: David Blum
Author: James Nicoll ORCID iD
Author: Guillaume Dorothee
Author: Delphine Boche ORCID iD

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