Work

Localization, induction, and cellular effects of tau phosphorylated at threonine 2171

Year: 2023

Type: article

Abstract: ABSTRACT Introduction Tau phosphorylation at T217 is a promising AD biomarker, but its functional consequences were unknown. Methods Human brain and cultured mouse neurons were analyzed by immunoblotting and immunofluorescence for total tau, tau pT217 , tau pT181 , tau pT231 and tau pS396/pS404 . dSTORM super resolution microscopy was used to localize tau pT217 in cultured neurons. EGFP-tau was expressed in fibroblasts as wild type and T217E pseudo-phosphorylated tau, and fluorescence recovery after photobleaching (FRAP) reported tau turnover rates on microtubules. Results In brain, tau pT217 appears in neurons at Braak stages I-II, becomes more prevalent later and co-localizes partially with other phospho-tau epitopes. In cultured neurons tau pT217 , is increased by extracellular tau oligomers (xcTauOs), and is associated with developing post-synaptic sites. FRAP recovery was fastest for EGFP-tau T217E . Conclusion Tau pT217 increases in brain as AD progresses and is induced by xcTauOs. Post-synaptic tau pT217 suggests a role for T217 phosphorylation in synapse impairment. T217 phosphorylation reduces tau’s affinity for microtubules.

Source: Alzheimer s & Dementia

DOI: 10.1002/alz.12892

Authors: Binita Rajbanshi, Anuj Guruacharya, James W. Mandell, George S. Bloom

Institutions: University of Virginia, Software Carpentry

Language: English

Topic: Alzheimer's disease research and treatments

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,000