Increased clusterin (apolipoprotein J) expression in human and mouse brains infected with transmissible spongiform encephalopathies

Kensuke Sasaki, Katsumi Doh-ura, James W. Ironside, Toru Iwaki

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Abstract

Clusterin (apolipoprotein J), a multifunctional protein involved in amyloidogenesis in Alzheimer's disease, was studied immunohistochemically in both human transmissible spongiform encephalopathies (TSEs) and a mouse model of human TSE. Clusterin immunoreactivity was co-localized with plaque-type deposits but not with punctate-type prion protein (PrP) deposits in human TSEs. On the other hand, clusterin-positive astrocytes were readily demonstrated in the regions of punctate PrP deposits, but not around plaque PrP deposits despite the presence of surrounding astrocytes. Clusterin expression in astrocytes was not disease specific, but the punctate immunoreactivity for clusterin was more prominently demonstrated in TSEs with punctate PrP deposits. Serial analysis in the mouse model of human TSE revealed that clusterin expression in astrocytes was enhanced in the lesions with punctate-type PrP deposits during the disease progression. Thus, the induction of clusterin expression in astrocytes could be more enhanced by punctate-type PrP deposits than by plaque-type deposits. The clusterin molecules co-localized in plaque PrP deposits might be derived not from surrounding astrocytes but from other resources such as cerebrospinal fluid and blood plasma, both of which contain clusterin in significant amounts. Taken together with previously reported findings of the anti-amyloidogenic property in clusterin, our findings suggest that clusterin may be induced as one of the important molecules participating in the neurodegeneration caused by abnormally deposited Prp.

Original languageEnglish
Pages (from-to)199-208
Number of pages10
JournalActa neuropathologica
Volume103
Issue number3
DOIs
Publication statusPublished - Dec 1 2002

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All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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