Immunohistochemical localization of advanced glycation end products, pentosidine, and carboxymethyllysine in lipofuscin pigments of Alzheimer's disease and aged neurons

Katsunori Horie, Toshio Miyata, Takeshi Yasuda, Akinori Takeda, Yoshinari Yasuda, Kenji Maeda, Gen Sobue, Kiyoshi Kurokawa

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

Lipofuscins are intracellular fluorescent pigments accumulating in the central nervous system (CNS) with aging and degenerative processes such as Alzheimer's disease (AD). Although they are thought to be lipid peroxidation products derived from malondialdehyde, their biogenesis remains controversial. We further characterize the chemical nature of lipofuscins in brain tissues from AD patients and normal aged subjects. Advanced glycation end products (AGEs), pentosidine and carboxymethyllysine (CML), were identified by appropriate specific antibodies. They have physicochemical properties similar to those of lipofuscin and also increase with aging. Pentosidine and CML were identified in the neuronal perikarya and the extraneuroperikaryal deposits of both the AD and aged brain. Pentosidine, but not CML, was present in the fiber-like structure within the neuropil and the core of classical senile plaque. In the brain of young subjects without CNS disease, pentosidine and CML staining was faint. Pentosidine and CML co-localized with lipofuscin pigments in the neuronal perikarya of both the AD and aged brain. We demonstrate for the first time that lipofuscin is constituted not only of lipid peroxidation products but also from glycation products which may be the origin of fluorescent pigments. Lipofuscins should thus be considered as fluorescent pigments generated by lipid- and sugar-derived Schiff base-protein polymers.

Original languageEnglish
Pages (from-to)327-332
Number of pages6
JournalBiochemical and biophysical research communications
Volume236
Issue number2
DOIs
Publication statusPublished - 1997 Jul 18
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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