Lipid peroxidation and advanced glycation end products in the brain in normal aging and in Alzheimer's disease.
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 product, N(epsilon)-(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.
Department of Neurology, Nagoya University School of Medicine, Tsurumai 65, Showa, Nagoya 466-8550, Japan.
Rika
R
Dei
Akinori
A
Takeda
Hisayoshi
H
Niwa
Mei
M
Li
Yuji
Y
Nakagomi
Masaki
M
Watanabe
Toshiaki
T
Inagaki
Yukihiko
Y
Washimi
Yoshinari
Y
Yasuda
Katsunori
K
Horie
Toshio
T
Miyata
Gen
G
Sobue
D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D017127:Glycation End Products, Advanced / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D008239:Lysine / Q000031:analogs & derivatives / Q000276:immunology / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000276:immunology / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress
D017127:Glycation End Products, Advanced; D008315:Malondialdehyde; C048496:N(6)-carboxymethyllysine; D008239:Lysine