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Open Access 01-12-2013 | Research

Extensive deamidation at asparagine residue 279 accounts for weak immunoreactivity of tau with RD4 antibody in Alzheimer’s disease brain

Authors: Ayaho Dan, Muneaki Takahashi, Masami Masuda-Suzukake, Fuyuki Kametani, Takashi Nonaka, Hiromi Kondo, Haruhiko Akiyama, Takao Arai, David MA Mann, Yuko Saito, Hiroyuki Hatsuta, Shigeo Murayama, Masato Hasegawa

Published in: Acta Neuropathologica Communications | Issue 1/2013

Abstract

Background

Intracytoplasmic inclusions composed of filamentous tau proteins are defining characteristics of neurodegenerative tauopathies, but it remains unclear why different tau isoforms accumulate in different diseases and how they induce abnormal filamentous structures and pathologies. Two tau isoform-specific antibodies, RD3 and RD4, are widely used for immunohistochemical and biochemical studies of tau species in diseased brains.

Results

Here, we show that extensive irreversible post-translational deamidation takes place at asparagine residue 279 ( N279) in the RD4 epitope of tau in Alzheimer’s disease (AD), but not corticobasal degeneration (CBD) or progressive supranuclear palsy (PSP), and this modification abrogates the immunoreactivity to RD4. An antiserum raised against deamidated RD4 peptide specifically recognized 4R tau isoforms, regardless of deamidation, and strongly stained tau in AD brain. We also found that mutant tau with N279D substitution showed reduced ability to bind to microtubules and to promote microtubule assembly.

Conclusion

The biochemical and structural differences of tau in AD from that in 4R tauopathies found in this study may therefore have implications for prion-like propagation of tau.

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Title: Extensive deamidation at asparagine residue 279 accounts for weak immunoreactivity of tau with RD4 antibody in Alzheimer’s disease brain
Authors: Ayaho Dan
Muneaki Takahashi
Masami Masuda-Suzukake
Fuyuki Kametani
Takashi Nonaka
Hiromi Kondo
Haruhiko Akiyama
Takao Arai
David MA Mann
Yuko Saito
Hiroyuki Hatsuta
Shigeo Murayama
Masato Hasegawa
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Acta Neuropathologica Communications / Issue 1/2013
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/2051-5960-1-54

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Extensive deamidation at asparagine residue 279 accounts for weak immunoreactivity of tau with RD4 antibody in Alzheimer’s disease brain

Abstract

Background

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusion

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