Journal Article

DZNE-2021-00937

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Contribution of the astrocytic tau pathology to synapse loss in progressive supranuclear palsy and corticobasal degeneration.

Briel, N. (First author)DZNE* ; Pratsch, K.DZNE* ; Roeber, S. ; Arzberger, T.DZNE* ; Herms, J. (Last author)DZNE*

2021
Wiley-Blackwell Oxford

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Please use a persistent id in citations: doi:10.1111/bpa.12914

Abstract: Primary 4-repeat tauopathies with frontotemporal lobar degeneration (FTLD) like Progressive Supranuclear Palsy (PSP) or Corticobasal Degeneration (CBD) show diverse cellular pathology in various brain regions. Besides shared characteristics of neuronal and oligodendroglial cytoplasmic inclusions of accumulated hyperphosphorylated tau protein (pTau), astrocytes in PSP and CBD contain pathognomonic pTau aggregates - hence, lending the designation tufted astrocytes (TA) or astrocytic plaques (AP), respectively. pTau toxicity is most commonly assigned to neurons, whereas the implications of astrocytic pTau for maintaining neurotransmission within the tripartite synapse of human brains is not well understood. We performed immunofluorescent synapse labeling and automated puncta quantification in the medial frontal gyrus (MFG) and striatal regions from PSP and CBD postmortem samples to capture morphometric synaptic alterations. This approach indicated general synaptic losses of both, excitatory and inhibitory bipartite synapses in the frontal cortex of PSP cases, whereas in CBD lower synapse densities were only related to astrocytic plaques. In contrast to tufted astrocytes in PSP, affected astrocytes in CBD could not preserve synaptic integrity within their spatial domains, when compared to non-affected internal astrocytes or astrocytes in healthy controls. These findings suggest a pTau pathology-associated role of astrocytes in maintaining connections within neuronal circuits, considered as the microscopic substrate of cognitive dysfunction in CBD. By contrasting astrocytic-synaptic associations in both diseases, we hereby highlight astrocytic pTau as an important subject of prospective research and as a potential cellular target for therapeutic approaches in the primary tauopathies PSP and CBD.

Keyword(s): Aged (MeSH) ; Aged, 80 and over (MeSH) ; Astrocytes: pathology (MeSH) ; Brain: pathology (MeSH) ; Corticobasal Degeneration: pathology (MeSH) ; Female (MeSH) ; Frontotemporal Lobar Degeneration: pathology (MeSH) ; Humans (MeSH) ; Inclusion Bodies: pathology (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Neurons: pathology (MeSH) ; Supranuclear Palsy, Progressive: metabolism (MeSH) ; Supranuclear Palsy, Progressive: pathology (MeSH) ; Tauopathies: pathology (MeSH) ; tau Proteins: metabolism (MeSH) ; astrocytic plaques ; corticobasal degeneration ; progressive supranuclear palsy ; synapse loss ; tauopathy ; tufted astrocytes

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Contributing Institute(s):

1. Translational Brain Research (AG Herms)
2. Neuropathology / Brainbank (Neuropathology / Brainbank)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2021

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Database coverage:
; ; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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