Contribution of the astrocytic tau pathology to synapse loss in progressive supranuclear palsy and corticobasal degeneration.
Aged
Aged, 80 and over
Astrocytes
/ pathology
Brain
/ pathology
Corticobasal Degeneration
/ pathology
Female
Frontotemporal Lobar Degeneration
/ pathology
Humans
Inclusion Bodies
/ pathology
Male
Middle Aged
Neurons
/ pathology
Supranuclear Palsy, Progressive
/ metabolism
Tauopathies
/ pathology
tau Proteins
/ metabolism
astrocytic plaques
corticobasal degeneration
progressive supranuclear palsy
synapse loss
tauopathy
tufted astrocytes
Journal
Brain pathology (Zurich, Switzerland)
ISSN: 1750-3639
Titre abrégé: Brain Pathol
Pays: Switzerland
ID NLM: 9216781
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
19
08
2020
accepted:
12
10
2020
pubmed:
23
10
2020
medline:
3
2
2022
entrez:
22
10
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33089580
doi: 10.1111/bpa.12914
pmc: PMC8412068
doi:
Substances chimiques
tau Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12914Informations de copyright
© 2020 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.
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