Clusterin associates specifically with aβ40 in alzheimer's disease brain tissue

David R. Howlett, Tibor Hortobágyi, Paul T. Francis

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Genome-wide association studies have pointed to clusterin (apolipoprotein J) as being linked to the occurrence of Alzheimer's disease (AD); studies have identified the protein as a possible biomarker. The association between clusterin and senile plaques in AD brain is well known, and clusterin levels in AD brain are 40% higher than that in control subjects. The present study investigates, immunohistochemically, the association between clusterin and Aβ peptides in AD and control cortex. A unique and specific association between clusterin and Aβ40 was observed in plaques in the cerebral cortex from AD subjects in that only plaques that contained Aβ40 showed clusterin immunoreactivity, while the many plaques with Aβ42 alone lacked clusterin labeling. Cerebrovascular Aβ in AD brain generally lacked Aβ42 but was positively labeled by both the Aβ40 and the clusterin antibodies. In control subjects, however, Aβ40 was absent from plaques, although very occasional plaques were found to be labeled by both the Aβ42 and the clusterin antibodies. Overall, in AD, but not aged control brain, clusterin was associated specifically with the Aβ40 form of Aβ in the brain. The lack of clusterin in association with Aβ42 may be a significant feature in neuronal loss and neurodegeneration in the disease state.

Original languageEnglish
Pages (from-to)623-632
Number of pages10
JournalBrain Pathology
Volume23
Issue number6
DOIs
Publication statusPublished - Nov 1 2013

Keywords

  • Alzheimer's disease
  • amyloid beta-protein
  • apolipoprotein J
  • biomarker
  • clusterin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)
  • Clinical Neurology

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