Objective: To systematically map and quantify MAPT expression in neurons, astrocytes and oligodendroglia across different brain regions to determine whether cell type and/or regional differences in MAPT expression occurs. MAPT expression in neurons and glia containing tau-immunopositive inclusions in progressive supranuclear palsy (PSP) was also investigated.

Background: Tau is a microtubule-associated protein encoded by the MAPT gene with well-known functions in neurons. In contrast, only low levels of tau protein have been identified in astrocytes and oligodendroglia in situ and in vivo, and its function in these cells is not completely understood. Tau is the most commonly deposited protein in ageing and neurodegenerative diseases, including PSP, where phosphorylated tau aggregates in neurons and glia. It is not known whether accumulation of phosphorylated tau inclusions are associated with altered MAPT expression in neurons or glia.

Method: 3 control cases without neurodegenerative pathology (3M, 74-77y) with short postmortem interval and 3 PSP patients (3M, 73-77y) who underwent medical assistance in dying were included. RNAseq was used to quantify MAPT expression across different cell types in controls and PSP. The anatomical distribution of MAPT transcripts in different cell types and brain regions was mapped using RNAscope, which was combined with AT8 immunofluorescence to determine MAPT gene expression in cellular cytopathologies in PSP.

Results: MAPT gene expression was found in neurons, oligodendroglia and astrocytes. MAPT transcripts revealed by RNAscope showed the highest volume density observed in neurons. Volume density of MAPT transcripts varied between brain regions and within each cell type suggesting distinct sub-populations of cells within neurons, oligodendroglia and astrocytes. In PSP, the presence of MAPT transcripts was confirmed in cells that contained phosphorylated tau inclusions, including neurofibrillary tangles, oligodendroglial coiled bodies, and tufted astrocytes.

Conclusion: Results from this study demonstrate that similar to neurons, oligodendroglia and astrocytes contain MAPT transcripts indicating that glia have MAPT protein expression that can potentially be phosphorylated and fibrillized into pathological inclusions, in addition to, or rather than being taken up by neurons. This study also highlights that MAPT gene expression in tau-containing cells is preserved in PSP.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cell-specific-mapt-gene-expression-is-preserved-in-tau-cytopathologies-in-progressive-supranuclear-palsy/