Clusterin Associates Specifically with A β40 in A lzheimer's Disease Brain Tissue

Abstract

Genome‐wide association studies have pointed to clusterin (apolipoprotein J) as being linked to the occurrence of A lzheimer'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 A β peptides in AD and control cortex. A unique and specific association between clusterin and A β40 was observed in plaques in the cerebral cortex from AD subjects in that only plaques that contained A β40 showed clusterin immunoreactivity, while the many plaques with A β42 alone lacked clusterin labeling. Cerebrovascular A β in AD brain generally lacked A β42 but was positively labeled by both the A β40 and the clusterin antibodies. In control subjects, however, A β40 was absent from plaques, although very occasional plaques were found to be labeled by both the A β42 and the clusterin antibodies. Overall, in AD, but not aged control brain, clusterin was associated specifically with the A β40 form of A β in the brain. The lack of clusterin in association with A β42 may be a significant feature in neuronal loss and neurodegeneration in the disease state.