3R and 4R tau isoforms in paired helical filaments in Alzheimer’s disease

Masato Hasegawa,Shigeo Murayama,Haruhiko Akiyama,Sayuri Watanabe,David M A Mann,Hiromi Kondo,Yuko Saito

doi:10.1007/s00401-013-1191-9

Abstract

3R and 4R tau isoforms in paired helical filaments in Alzheimer’s disease

Highlights

Paraffin sections of Alzheimer’s disease (AD) brains were treated with 10 μg/mL Proteinase K (Pro-K) for 30 min after autoclaving (Ac) and formic acid (FA) treatment
Ghost tangles and RD3−/RD4+ tangles and their processes became RD3-positive after Pro-K treatment (Fig. 1a, b), strongly suggesting that the RD3 epitope was buried in tau filaments of intracellular tangles and threads, and was exposed by Pro-K treatment
To confirm these findings biochemically, Sarkosylinsoluble fractions from two AD brains were treated with trypsin or Pro-K, immunoblotted with RD3, RD4, anti-4R and anti-pS396 (Fig. 1g–j)

Summary

Introduction

Watanabe Department of Neuropathology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Setagaya‐ku, Tokyo 156‐8506, Japan e-mail: hasegawa‐ms@igakuken.or.jp H. Kondo Histology Center, Tokyo Metropolitan Institute of Medical Science, Setagaya‐ku, Tokyo 156‐8506, Japan H. Akiyama Dementia Research Project, Tokyo Metropolitan Institute of Medical Science, Setagaya‐ku, Tokyo 156‐8506, Japan S. Murayama Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Itabashi‐ku, Tokyo 173‐0015, Japan presence of 4R tau in AD pathologies may be underestimated when RD4 is used.

Results

Conclusion