Astrocyte tau deposition in progressive supranuclear palsy is associated with dysregulation of MAPT transcription.

Publisher: BioMed Central Country of Publication: England NLM ID: 101610673 Publication Model: Electronic Cited Medium: Internet ISSN: 2051-5960 (Electronic) Linking ISSN: 20515960 NLM ISO Abbreviation: Acta Neuropathol Commun Subsets: MEDLINE

Original Publication: London : BioMed Central, [2013]-

Supranuclear Palsy, Progressive*/metabolism ; Supranuclear Palsy, Progressive*/pathology ; Supranuclear Palsy, Progressive*/genetics ; tau Proteins*/metabolism ; tau Proteins*/genetics ; Astrocytes*/metabolism ; Astrocytes*/pathology; Humans ; Aged ; Male ; Aged, 80 and over ; Female ; Middle Aged ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Alzheimer Disease/genetics ; Transcription, Genetic ; Brain/metabolism ; Brain/pathology

Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by 4R tau deposition in neurons as well as in astrocytes and oligodendrocytes. While astrocytic tau deposits are rarely observed in normal aging (so-called aging-related tau astrogliopathy, ARTAG) and Alzheimer's disease (AD), astrocytic tau in the form of tufted astrocytes is a pathognomonic hallmark of PSP. Classical biochemical experiments emphasized tau synthesis in neurons in the central nervous system, suggesting that astrocytic tau inclusions might be derived from uptake of extracellular neuronal-derived tau. However, recent single-nucleus RNAseq experiments highlight the fact that MAPT, the gene encoding tau, is also expressed by astrocytes, albeit in lower amounts. We, therefore, revisited the question of whether astrocyte-driven expression of tau might contribute to astrocytic tau aggregates in PSP by performing fluorescent in situ hybridization/immunohistochemical co-localization in human postmortem brain specimens from individuals with PSP and AD with ARTAG as well as normal controls. We find that, in PSP but not in AD, tau-immunoreactive astrocytes have higher levels of MAPT mRNA compared to astrocytes that do not have tau aggregates. These results suggest that astrocytic responses in PSP are unique to this tauopathy and support the possibility that fundamental changes in PSP astrocyte-endogenous mRNA biology contribute to increased synthesis of tau protein and underlies the formation of the astrocytic tau deposits characteristic of PSP.
(© 2024. The Author(s).)

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Bristol-Myers Squibb Bristol-Myers Squibb; P30 AG062421 United States AG NIA NIH HHS; Rainwater Charitable Foundation Rainwater Charitable Foundation; Harrison Gardner, Jr. Innovation Award Harrison Gardner, Jr. Innovation Award; P30AG062421 United States AG NIA NIH HHS

Keywords: Astrocytes; MAPT; Progressive supranuclear palsy; Tau; Tufted astrocytes

0 (tau Proteins)
0 (MAPT protein, human)

Date Created: 20240813 Date Completed: 20240814 Latest Revision: 20240816

20240816

PMC11323491

10.1186/s40478-024-01844-6

39138580