Codeposition of cystatin C with amyloid-β protein in the brain of alzheimer disease patients

Efrat Levy, Magdalena Sastre, Asok Kumar, Gloria Gallo, Pedro Piccardo, Bernardino Ghetti, Fabrizio Tagliavini

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

Immunohistochemical analysis of brains of patients with Alzheimer disease (AD) revealed that the cysteine proteinase inhibitor cystatin C colocalizes with amyloid β-protein (Aβ) in parenchymal and vascular amyloid deposits. No evidence of cerebral hemorrhage was observed in any of the brains studied. Immunoelectron microscopy demonstrated dual staining of amyloid fibrils with anti-Aβ and anti-cystatin C antibodies. Cystatin C immunoreactivity was also observed in amyloid deposits in the brain of transgenic mice overexpressing human β amyloid precursor protein. Massive deposition of the variant cystatin C in the cerebral vessels of patients with the Icelandic form of hereditary cerebral hemorrhage with amyloidosis is thought to be responsible for the pathological processes leading to stroke. Anti-cystatin C antibodies strongly labeled pyramidal neurons within cortical layers most prone to amyloid deposition in the brains of AD patients. Immunohistochemistry with antibodies against the carboxyl-terminus of Aβx-42 showed intracellular immunoreactivity in the same neuronal subpopulation. It remains to be established whether the association of cystatin C to Aβ plays a primary role in amyloidogenesis of AD or is a late event in which the protein is bound to the previously formed Aβ amyloid fibrils.

Original languageEnglish
Pages (from-to)94-104
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Volume60
Issue number1
Publication statusPublished - 2001

Fingerprint

Amyloidogenic Proteins
Cystatin C
Brain Diseases
Alzheimer Disease
Amyloid
Amyloid Plaques
Antibodies
Familial Cerebral Amyloid Angiopathy
Brain
Cysteine Proteinase Inhibitors
Serum Amyloid A Protein
Immunoelectron Microscopy
Amyloid beta-Protein Precursor
Pyramidal Cells
Cerebral Hemorrhage
Pathologic Processes
Transgenic Mice
Blood Vessels
Immunohistochemistry
Stroke

Keywords

  • β amyloid precursor protein (βAPP)
  • Alzheimer disease (AD)
  • Amyloid β-protein (Aβ)
  • Cerebral amyloid angiopathy (CAA)
  • Hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D)
  • Hereditary cerebral hemorrhage with amyloidosis, Icelandic type (HCHWA-I)

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Codeposition of cystatin C with amyloid-β protein in the brain of alzheimer disease patients. / Levy, Efrat; Sastre, Magdalena; Kumar, Asok; Gallo, Gloria; Piccardo, Pedro; Ghetti, Bernardino; Tagliavini, Fabrizio.

In: Journal of Neuropathology and Experimental Neurology, Vol. 60, No. 1, 2001, p. 94-104.

Research output: Contribution to journalArticle

Levy, Efrat ; Sastre, Magdalena ; Kumar, Asok ; Gallo, Gloria ; Piccardo, Pedro ; Ghetti, Bernardino ; Tagliavini, Fabrizio. / Codeposition of cystatin C with amyloid-β protein in the brain of alzheimer disease patients. In: Journal of Neuropathology and Experimental Neurology. 2001 ; Vol. 60, No. 1. pp. 94-104.
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