Waller, R. orcid.org/0000-0001-5815-8829, Narramore, R., Simpson, J.E. orcid.org/0000-0002-3753-4271 et al. (12 more authors) (2021) Heterogeneity of cellular inflammatory responses in ageing white matter and relationship to alzheimer’s and small vessel disease pathologies. Brain Pathology, 31 (3). e12928. ISSN 1015-6305
Abstract
White matter lesions (WML) are common in the ageing brain, often arising in a field effect of diffuse white matter abnormality. Although WML are associated with cerebral small vessel disease (SVD) and Alzheimer’s disease (AD), their cause and pathogenesis remain unclear. The current study tested the hypothesis that different patterns of neuroinflammation are associated with SVD compared to AD neuropathology by assessing the immunoreactive profile of the microglial (CD68, IBA1 and MHC‐II) and astrocyte (GFAP) markers in ageing parietal white matter (PARWM) obtained from the Cognitive Function and Ageing Study (CFAS), an ageing population‐representative neuropathology cohort.
Glial responses varied extensively across the PARWM with microglial markers significantly higher in the subventricular region compared to either the middle‐zone (CD68 P=0.028, IBA1 P<0.001, MHC‐II P<0.001) or subcortical region (CD68 P=0.002, IBA1 P<0.001, MHC‐II P<0.001). Clasmatodendritic (CD) GFAP+ astrocytes significantly increased from the subcortical to the subventricular region (P<0.001), whilst GFAP+ stellate astrocytes significantly decreased (P<0.001). Cellular reactions could be grouped into two distinct patterns: an immune response associated with MHC‐II/IBA1 expression and CD astrocytes; and a more innate response characterised by CD68 expression associated with WML. White matter neuroinflammation showed weak relationships to measures of SVD, but not to measures of AD neuropathology.
In conclusion, glial responses vary extensively across the PARWM with diverse patterns of white matter neuroinflammation. Although these findings support a role for vascular factors in the pathogenesis of age‐related white matter neuroinflammation, additional factors other than SVD and AD pathology may drive this. Understanding the heterogeneity in white matter neuroinflammation will be important for the therapeutic targeting of age‐associated white matter damage.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 International Society of Neuropathology. This is an author-produced version of a paper subsequently published in Brain Pathology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | white matter lesions; small vessel disease; neuroinflammation; dementia; epidemiological neuropathology |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number MEDICAL RESEARCH COUNCIL MR/J004308/1 ALZHEIMER'S SOCIETY 242 (AS-PG-14-015) ALZHEIMER'S SOCIETY AS-PG-17-007 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 04 Jan 2021 17:10 |
Last Modified: | 01 Feb 2022 09:29 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1111/bpa.12928 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:169383 |