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Mesial temporal astrocyte tau pathology in the MRC-CFAS ageing brain cohort
1Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK.
Background:
Glial tau pathology is seen in certain tauopathies and in ageing. We determined its frequency in ageing mesial temporal lobe and its relationship to other tau pathologies in the MRC-CFAS population-representative neuropathology cohort.
Methods:
Mesial temporal lobe, including hippocampus, amygdala, entorhinal cortex and white matter, was examined using immunohistochemistry with the AT8 antibody to phospho-tau and RD3 and RD4 antibodies to 3R and 4R tau isoforms. Gallyas silver stain was used to detect fibrillar aggregates.
Results:
Thorn-shaped astrocytes (TSA), positive with AT8, RD4 and Gallyas, were present in 49% of cases. They were particularly prevalent in subpial, periventricular and white matter perivascular locations and were less frequent in grey matter. Coiled bodies were seen in 18.8%. TSA were not related to Braak neurofibrillary tangle or hippocampal tangle pathology stages. TSA in grey matter were associated with coiled bodies (p = 0.011) and argyrophilic grains (p = 0.048), which were identified in 11.5% of cases. They did not correlate with dementia.
Conclusions:
Astrocyte tau pathology is common in the ageing mesial temporal lobe. Its formation is independent of Alzheimer-type pathology. It is a 4R tauopathy, which may form part of a mesial temporal age-related 4R tauopathy that includes oligodendroglial tau and argyrophilic grains.
Insights
Glial tau pathology, specifically thorn-shaped astrocytes (TSA), is common in the aging brain. This 4R tauopathy is independent of Alzheimer's disease and may be linked to other age-related tau conditions.
Area of Science:
- Neuroscience
- Neuropathology
- Aging Research
Background:
- Glial tau pathology is observed in tauopathies and during aging.
- Its prevalence and associations in the aging mesial temporal lobe require further investigation.
Purpose of the Study:
- To determine the frequency of glial tau pathology in the aging mesial temporal lobe.
- To investigate the relationship between glial tau pathology and other tau pathologies in a population-representative cohort.
Main Methods:
- Immunohistochemistry using AT8, RD3, and RD4 antibodies for tau isoforms.
- Gallyas silver stain to detect fibrillar tau aggregates.
- Examination of mesial temporal lobe structures including hippocampus, amygdala, entorhinal cortex, and white matter.
Main Results:
- Thorn-shaped astrocytes (TSA), a form of glial tau pathology, were found in 49% of cases, predominantly in white matter and subpial regions.
- TSA were not associated with Braak neurofibrillary tangle stages but correlated with coiled bodies and argyrophilic grains in grey matter.
- Glial tau pathology did not correlate with dementia status.
Conclusions:
- Astrocyte tau pathology is a frequent finding in the aging mesial temporal lobe.
- This pathology appears independent of Alzheimer's disease-type pathology.
- It represents a 4R tauopathy and may be part of an age-related tauopathy spectrum including oligodendroglial tau and argyrophilic grains.
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