Novel quantitative analysis of abnormal phosphorylated tau

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K18366
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Tokyo Metropolitan University
• Principal Investigator: KIMURA TAEKO 首都大学東京, 理工学研究科, 特任研究員 (60748820)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: タウ / リン酸化 / Phos-Tag SDS-PAGE法 / Cdk5 / ヒト患者脳 / タウオパチー

Outline of Final Research Achievements

Tau is hyperphosphorylated in the brains of patients with tauopathies, such as Alzheimer's disease. However, neither the mechanism of hyperphosphorylation nor its contribution to pathogenesis is known. I applied the Phos-tag SDS-PAGE. Here, I found ~12 phosphorylation isotypes of tau in culture cells with different combinations of phosphorylation at Thr181, Ser202, Thr231, Ser235 and Ser404. These phosphorylation sites were similar to tau phosphorylated in mouse brains. In normal elderly human brains, nonphosphorylated 0N3R and 0N4R tau were most abundant. A slightly higher phosphorylation of tau, which may represent the early step of hyperphosphorylation, was increased in Alzheimer disease patients at Braak stage V. Tau was pelleted by centrifugation, and sarkosyl-soluble tau in either Alzheimer disease or corticobasal degeneration brains showed phosphorylation profiles similar to tau in normal human brain, suggesting that hyperphosphorylation occurs in aggregated tau.

Free Research Field

神経化学