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

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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 1993

Fingerprint

Guam
Cystatins
Cathepsins
Parkinsonian Disorders
Neurofibrillary Tangles
Amyloid
Amyloid Plaques
Dementia
Hippocampus
Alzheimer Disease
Peptide Hydrolases
Cathepsin B
Cathepsin H
Cathepsin C
Cathepsin L
Protein Denaturation
Cystatin C
Neurites
Dendrites
Lysosomes

Keywords

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Anatomy

Cite this

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title = "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",
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.",
keywords = "Alzheimer's disease, Cathepsins, Cystatins, Immunohistochemistry, Parkinsonism-dementia complex on Guam",
author = "Kunio Ii and Hidehumi Ito and Eiki Kominami and Asao Hirano",
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T1 - 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

AU - Ii, Kunio

AU - Ito, Hidehumi

AU - Kominami, Eiki

AU - Hirano, Asao

PY - 1993/5

Y1 - 1993/5

N2 - 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.

AB - 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.

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KW - Cystatins

KW - Immunohistochemistry

KW - Parkinsonism-dementia complex on Guam

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