TY  - JOUR
AU  - Briel, Nils
AU  - Pratsch, Katrin
AU  - Roeber, Sigrun
AU  - Arzberger, Thomas
AU  - Herms, Jochen
TI  - Contribution of the astrocytic tau pathology to synapse loss in progressive supranuclear palsy and corticobasal degeneration.
JO  - Brain pathology
VL  - 31
IS  - 4
SN  - 1750-3639
CY  - Oxford
PB  - Wiley-Blackwell
M1  - DZNE-2021-00937
SP  - e12914
PY  - 2021
AB  - 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.
KW  - Aged
KW  - Aged, 80 and over
KW  - Astrocytes: pathology
KW  - Brain: pathology
KW  - Corticobasal Degeneration: pathology
KW  - Female
KW  - Frontotemporal Lobar Degeneration: pathology
KW  - Humans
KW  - Inclusion Bodies: pathology
KW  - Male
KW  - Middle Aged
KW  - Neurons: pathology
KW  - Supranuclear Palsy, Progressive: metabolism
KW  - Supranuclear Palsy, Progressive: pathology
KW  - Tauopathies: pathology
KW  - tau Proteins: metabolism
KW  - astrocytic plaques (Other)
KW  - corticobasal degeneration (Other)
KW  - progressive supranuclear palsy (Other)
KW  - synapse loss (Other)
KW  - tauopathy (Other)
KW  - tufted astrocytes (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:33089580
C2  - pmc:PMC8412068
DO  - DOI:10.1111/bpa.12914
UR  - https://pub.dzne.de/record/155769
ER  -