Lipid peroxidation and advanced glycation end products in the brain in normal aging and in Alzheimer's disease

Rika Dei, Akinori Takeda, Hisayoshi Niwa, Mei Li, Yuji Nakagomi, Masaki Watanabe, Toshiaki Inagaki, Yukihiko Washimi, Yoshinari Yasuda, Katsunori Horie, Toshio Miyata, Gen Sobue

Research output: Contribution to journalArticlepeer-review

122 Citations (Scopus)

Abstract

The cellular distribution of malondialdehyde (MDA) was assessed immunohistochemically in brain specimens from young and normal elderly subjects as well as patients with Alzheimer's disease (AD). MDA was increased in the cytoplasm of neurons and astrocytes in both normal aging and AD, but was rarely detected in normal young subjects. By electron microscopic immunohistochemistry, neuronal MDA formed cap-like linear deposits associated with lipofuscin, while glial MDA deposits surrounded the vacuoles in a linear distribution. In the hippocampus, neuronal and glial MDA deposition was marked in the CA4 region but mild in CA1. By examination of serial sections stained with anti-MDA and antibodies against an advanced glycation end produc t, NE-(carboxymethyl)lysine (CML), neuronal and glial MDA deposition was colocalized with CML in AD, but only neuronal MDA was colocalized with CML in normal aged brains. Glial MDA, although abundant in the aged brain, typically was not colocalized with CML. In AD cases, MDA was colocalized with tau protein in CA2 hippocampal neurons; such colocalization was rare in CA1. MDA also was stained in cores of senile plaques. Thus, while both MDA and CML accumulate under oxidative stress, CML accumulation is largely limited to neurons, in normal aging, while MDA also accumulates in glia. In AD, both MDA and CML are deposited in both astrocytes and neurons.

Original languageEnglish
Pages (from-to)113-122
Number of pages10
JournalActa neuropathologica
Volume104
Issue number2
DOIs
Publication statusPublished - 2002

Keywords

  • Advanced glycation end product
  • Lipid Peroxidation
  • Malondialdehyde
  • N-(carboxymethyl)lysine
  • Oxidative stress

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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