Tau Ser208 phosphorylation promotes aggregation and reveals neuropathologic diversity in Alzheimer's disease and other tauopathies.
AT8
Alzheimer’s disease
CP13
Microtubule binding
Microtubule-associated protein tau (MAPT)
Neurodegeneration
Neurofibrillary tangle
Prion-like seeding
Protein aggregation
Tauopathy
tau
Journal
Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673
Informations de publication
Date de publication:
22 06 2020
22 06 2020
Historique:
received:
23
04
2020
accepted:
12
06
2020
entrez:
24
6
2020
pubmed:
24
6
2020
medline:
29
5
2021
Statut:
epublish
Résumé
Tau protein abnormally aggregates in tauopathies, a diverse group of neurologic diseases that includes Alzheimer's disease (AD). In early stages of disease, tau becomes hyperphosphorylated and mislocalized, which can contribute to its aggregation and toxicity. We demonstrate that tau phosphorylation at Ser208 (pSer208) promotes microtubule dysfunction and tau aggregation in cultured cells. Comparative assessment of the epitopes recognized by antibodies AT8, CP13, and 7F2 demonstrates that CP13 and 7F2 are specific for tau phosphorylation at Ser202 and Thr205, respectively, independently of the phosphorylation state of adjacent phosphorylation sites. Supporting the involvement of pSer208 in tau pathology, a novel monoclonal antibody 3G12 specific for tau phosphorylation at Ser208 revealed strong reactivity of tau inclusions in the brains of PS19 and rTg4510 transgenic mouse models of tauopathy. 3G12 also labelled neurofibrillary tangles in brains of patients with AD but revealed differential staining compared to CP13 and 7F2 for other types of tau pathologies such as in neuropil threads and neuritic plaques in AD, tufted astrocytes in progressive supranuclear palsy and astrocytic plaques in corticobasal degeneration. These results support the hypothesis that tau phosphorylation at Ser208 strongly contributes to unique types of tau aggregation and may be a reliable marker for the presence of mature neurofibrillary tangles.
Identifiants
pubmed: 32571418
doi: 10.1186/s40478-020-00967-w
pii: 10.1186/s40478-020-00967-w
pmc: PMC7310041
doi:
Substances chimiques
MAPT protein, human
0
tau Proteins
0
Serine
452VLY9402
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
88Subventions
Organisme : NIA NIH HHS
ID : F30 AG063446
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG047266
Pays : United States
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