Garwood, C.J., Ratcliffe, L.E., Simpson, J.E. et al. (3 more authors) (2017) Review: Astrocytes in Alzheimer's disease and other age-associated dementias: a supporting player with a central role. Neuropathology and Applied Neurobiology, 43 (4). pp. 281-298. ISSN 1365-2990
Abstract
Astrocytes have essential roles in the central nervous system and are also implicated in the pathogenesis of neurodegenerative disease. Forming non-overlapping domains, astrocytes are highly complex cells. Immunohistochemistry to a variety of proteins can be used to study astrocytes in tissue, labelling different cellular components and subpopulations, including GFAP, ALDH1L1, CD44, NDRG2 and amino acid transporters, but none of these label the entire astrocyte population. Increasing heterogeneity is recognised in the astrocyte population, a complexity that is relevant both to their normal function and pathogenic roles. They are involved in neuronal support, as active components of the tripartite synapse and in cell interactions within the neurovascular unit, where they are essential for blood brain barrier maintenance and neurovascular coupling. Astrocytes change with age, and their responses may modulate the cellular effects of neurodegenerative pathologies, which alone do not explain all of the variance in statistical models of neurodegenerative dementias. Astrocytes respond to both the neurofibrillary tangles and plaques of Alzheimer’s disease, to hyperphosphorylated tau and Aβ, eliciting an effect which may be neuroprotective or deleterious. Astrocyte hypertrophy, in the form of gliosis, occurs, but also astrocyte injury and atrophy. Loss of normal astrocyte functions may contribute to reduced support for neurons and dysfunction of the neurovascular unit. Understanding how astrocytes contribute to dementia requires an understanding of the underlying heterogeneity of astrocyte populations, and the complexity of their responses to pathology. Enhancing the supportive and neuroprotective components of the astrocyte response has potential translational applications in therapeutic approaches to dementia.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 British Neuropathological Society. This is an author produced version of a paper subsequently published in Neuropathology and Applied Neurobiology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Astrocytes; dementia; Alzheimer’s disease; neurovascular unit; neurodegeneration |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number ALZHEIMER'S SOCIETY 248 (AS-JF-14-001) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 20 Jul 2016 11:46 |
Last Modified: | 20 Mar 2018 10:25 |
Published Version: | https://doi.org/10.1111/nan.12338 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1111/nan.12338 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:102633 |