RD3
Protein RD3 (Retinal degeneration protein 3) [C1orf36]
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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. 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. 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. 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.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Apolipoproteins E
- Astrocytes
- Brain
- Brain Chemistry
- Cadaver
- Cell Shape
- Cohort Studies
- Disease Progression
- Female
- Genotype
- Hippocampus
- Humans
- Immunohistochemistry
- Male
- Neuroglia
- Oligodendroglia
- Silver Staining
- tau Proteins
Deposits of abnormally phosphorylated tau protein are found in numerous neurodegenerative disorders; the 'tauopathies', which include Alzheimer's and Pick's diseases, but tau pathology is also found in the ageing brain. Variation in tau pathology in brain ageing and its relationship to development of tauopathies and cognitive impairment remains unclear. We aimed to determine the extent and pattern of spread of tau pathology in the hippocampus, a susceptible region important in dementia and milder states of memory impairment, using hippocampal samples from the elderly population-based Medical Research Council Cognitive Function and Ageing Study neuropathology cohort. Tau deposition was assessed in hippocampal anatomical sub-regions using the AT8 antibody to phosphorylated tau and isoform-specific antibodies to 3 and 4-repeat tau (RD3 and RD4). Abeta pathology was also assessed. In this population sample, which includes the full ageing spectrum from individuals with no cognitive impairment to those with dementia satisfying clinico-pathology criteria for Alzheimer's disease, we have demonstrated a high prevalence at death of tau pathology. AT8, Abeta, RD3 and RD4 showed similar regional distribution and increased RD3 was noted in late-stage ghost tangles. Abeta was shown to be a poor explanatory variable for tau pathology. Tau deposition progressed in a hierarchical manner. Hippocampal input regions and projection zones (such as lateral entorhinal cortex, CA1/subiculum border and outer molecular layer of dentate) were initially affected, with anterograde progression though the hippocampal circuitry. Six hippocampal tau anatomical stages were defined, each linking projectionally to their adjacent stages, suggesting spread of tau malfunction through neuroanatomical pathways in hippocampal ageing. These stages were significantly associated with dementia, and may provide a clinically useful tool in the clinico-pathological assessment of dementia and mild cognitive impairment.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Alzheimer Disease
- Amyloid beta-Peptides
- Chi-Square Distribution
- Cognition
- Disease Progression
- Entorhinal Cortex
- Female
- Hippocampus
- Humans
- Immunohistochemistry
- Longitudinal Studies
- Male
- Neural Pathways
- tau Proteins