Clusterin Associates Specifically with Aβ40 in Alzheimer's Disease Brain Tissue

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 A peptides in AD and control cortex. A unique and specific association between clusterin and A40 was observed in plaques in the cerebral cortex from AD subjects in that only plaques that contained A40 showed clusterin immunoreactivity, while the many plaques with A42 alone lacked clusterin labeling. Cerebrovascular A in AD brain generally lacked A42 but was positively labeled by both the A40 and the clusterin antibodies. In control subjects, however, A40 was absent from plaques, although very occasional plaques were found to be labeled by both the A42 and the clusterin antibodies. Overall, in AD, but not aged control brain, clusterin was associated specifically with the A40 form of A in the brain. The lack of clusterin in association with A42 may be a significant feature in neuronal loss and neurodegeneration in the disease state.