Abnormal distribution of cathepsin proteinases and endogenous inhibitors (cystatins) in the hippocampus of patients with Alzheimer's disease, parkinsonism-dementia complex on Guam, and senile dementia and in the aged

Kunio Ii, Hidehumi Ito, Eiki Kominami, Asao Hirano

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

The immunolocalization of cathepsins B(CB), H and L and cystatins α(C α) and β(Cβ) were examined in the hippocampus of cases of sporadic Alzheimer's disease (12 cases), parkinsonism-dementia complex on Guam (eight cases), senile dementia of Alzheimer type (two cases), aged subjects with marked senile change (one case) and controls (12 cases, including six normal subjects). CB was lower in most nerve cells in patients than in controls, but markedly increased at the sites of intracellular neurofibrillary tangles (NFTs) and degenerative neurites and/or dendrites in and outside senile plaques (SPs), indicating its close involvement in the metabolisms of various proteins in NFT and SPs. Abundant C α and C β were demonstrated in SP amyloid, suggesting that they are amyloid constituents or co-exist with amyloid. The present study indicated that CB, C α and C β are closely involved in abnormal protein metabolism in NFTs and SP amyloid and suggested that degeneration or denaturation of intracellular proteins, including substrates for proteases and lysosomes, from some acquired cause, results in absolute and/or relative overload for these proteolytic systems, including their inhibitors. This results in incomplete and/or abnormal proteolysis related to NFT and/or amyloid formation.

Original languageEnglish (US)
Pages (from-to)185-194
Number of pages10
JournalVirchows Archiv A Pathological Anatomy and Histopathology
Volume423
Issue number3
DOIs
StatePublished - May 1 1993

Keywords

  • Alzheimer's disease
  • Cathepsins
  • Cystatins
  • Immunohistochemistry
  • Parkinsonism-dementia complex on Guam

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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