Distinct phosphorylation profiles of tau in brains of patients with different tauopathies

NEUROBIOLOGY OF AGING

卷:108

Article

Samimi, Nastaran^1,2,3  Sharma, Govinda^1,8  Kimura, Taeko^1,7  Matsubara, Tomoyasu⁴  Huo, Anni^1,9  Chiba, Kurumi¹  Saito, Yuko⁴  Murayama, Shigeo⁴  Akatsu, Hiroyasu^5,6  Hashizume, Yoshio⁶  Hasegawa, Masato⁷  Shahpasand, Koorosh²  Ando, Kanae¹  Hisanaga, Shin-ichi^1,7 

[1] Tokyo Metropolitan Univ, Grad Sch Sci, Dept Biol Sci, Hachioji, Tokyo, Japan

[2] ACECR, Dept Brain & Cognit Sci, Cell Sci Res Ctr, Royan Inst Stem Cell Biol & Technol, Tehran, Iran

[3] Fasa Univ Med Sci, Noncommunicable Dis Res Ctr, Fasa, Iran

[4] Tokyo Metropolitan Geriatr Hosp & Inst Gerontol, Dept Neuropathol, Brain Bank Aging Res, Itabashi Ku, Tokyo, Japan

[5] Nagoya City Univ, Dept Community Based Med Educ, Grad Sch Med, Mizuho Ku, Nagoya, Aichi, Japan

[6] Fukushimura Hosp, Inst Neuropathol, Toyohashi, Aichi, Japan

[7] Tokyo Metropolitan Inst Med Sci, Dept Dementia & Higher Brain Funct, Setagaya Ku, Tokyo, Japan

[8] Univ Calgary, Dept Med Genet, Calgary, AB T2N 1N4, Canada

[9] Tokyo Metropolitan Inst Med Sci, Prot Metab Project, Setagaya Ku, Tokyo 1568506, Japan

关键词: Tau;    Tauopathy;    Phosphorylation;    Cis p-tau;    Pin1;    Phos-tag SDS-PAGE;   

DOI  :  10.1016/j.neurobiolaging.2021.08.011

来源: Elsevier

【 摘 要 】

Tauopathies are neurodegenerative diseases that are characterized by pathological accumulation of tau protein. Tau is hyperphosphorylated in the brain of tauopathy patients, and this phosphorylation is proposed to play a role in disease development. However, it has been unclear whether phosphorylation is different among different tauopathies. Here, we investigated the phosphorylation states of tau in several tauopathies, including corticobasal degeneration, Pick's disease, progressive supranuclear palsy (PSP), argyrophilic grain dementia (AGD) and Alzheimer's disease (AD). Analysis of tau phosphorylation profiles using Phos-tag SDS-PAGE revealed distinct phosphorylation of tau in different tauopathies, whereas similar phosphorylation patterns were found within the same tauopathy. For PSP, we found 2 distinct phosphorylation patterns suggesting that PSP may consist of 2 different related diseases. Immunoblotting with anti-phospho-specific antibodies showed different site-specific phosphorylation in the temporal lobes of patients with different tauopathies. AD brains showed increased phosphorylation at Ser202, Thr231 and Ser235, Pick's disease brains showed increased phospho-Ser202, and AGD brains showed increased phospho-Ser396. The cis conformation of the peptide bond between phospho-Thr231 and Pro232 (cis ptau) was increased in AD and AGD. These results indicate that while tau is differently phosphorylated in tauopathies, a similar pathological mechanism may occur in AGD and AD patients. The present data provide useful information regarding tau pathology and diagnosis of tauopathies. (c) 2021 Elsevier Inc. All rights reserved.

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