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Open Access 01-12-2015 | Research

Incidence and extent of TDP-43 accumulation in aging human brain

Authors: Akiko Uchino, Masaki Takao, Hiroyuki Hatsuta, Hiroyuki Sumikura, Yuta Nakano, Akane Nogami, Yuko Saito, Tomio Arai, Kazutoshi Nishiyama, Shigeo Murayama

Published in: Acta Neuropathologica Communications | Issue 1/2015

Abstract

Introduction

The transactivation response element DNA-binding protein 43 kDa (TDP-43) is a major component of the ubiquitin-positive and tau-negative inclusions in frontotemporal lobar degeneration and sporadic amyotrophic lateral sclerosis (ALS). TDP-43 may accumulate in cases of Alzheimer’s disease (AD), Lewy body disease (LBD), and argyrophilic grain disease (AGD). However, few studies have focused on the incidence and extent of TDP-43 deposition in aging.

Results

We analyzed 286 consecutive autopsy brains neuropathologically. Of these, 136 brains with pathologically minimal senile changes were designated as control elderly brains (78.5 ± 9.7 y). For comparison, we selected 29 AD, 11 LBD, and 11 AGD patients from this series of autopsy brains. Sections of the hippocampus, amygdala, medulla oblongata, and lumbar spinal cord were immunostained with anti-phosphorylated TDP-43 antibody (PSer409/410). TDP-43 immunoreactive structures were classified into four types: dystrophic neurites (DNs), neuronal or glial cytoplasmic inclusions, and intranuclear inclusions. TDP-43 immunoreactive structures were observed in 55/136 control elderly (40.0 %), 21/29 AD (72.4 %), 8/11 LBD (72.7 %), and 6/11 AGD (54.5 %) brains. TDP-43 immunoreactive structures in control elderly brains were mostly DNs. These DNs were predominantly present in the uncus of the anterior hippocampus over age 65. The frequency of cases with DNs in the amygdala of control elderly brains was less than that of AD, LBD, and AGD brains. The mean age at death was significantly higher in cases with TDP-43 immunoreactive structures than cases without them.

Conclusions

In conclusion, TDP-43 immunoreactive DNs may develop as a consequence of aging processes in the human brain. In particular, the uncus of the anterior hippocampus is an area highly susceptible to TDP-43 accumulation over age 65.

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Title: Incidence and extent of TDP-43 accumulation in aging human brain
Authors: Akiko Uchino
Masaki Takao
Hiroyuki Hatsuta
Hiroyuki Sumikura
Yuta Nakano
Akane Nogami
Yuko Saito
Tomio Arai
Kazutoshi Nishiyama
Shigeo Murayama
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Acta Neuropathologica Communications / Issue 1/2015
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/s40478-015-0215-1

At a glance: The STEP trials

Springer Medicine

Incidence and extent of TDP-43 accumulation in aging human brain

Abstract

Introduction

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Introduction

Results

Conclusions

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