POSSIBLE NEUROPROTECTIVE ROLE OF CLUSTERIN IN ALZHEIMERS-DISEASE - A QUANTITATIVE IMMUNOCYTOCHEMICAL STUDY

Clusterin is a secreted glycoprotein that is expressed in response to tissue injury both in peripheral organs and in the brain. Recent studi es have shown a substantial increase in clusterin mRNA in pyramidal ne urons of the hippocampus and the entorhinal cortex in Alzheimer's dise ase (AD), with clusterin immunoreactivity occurring in neuropil thread s, neurofibrillary tangles (NFT), and senile plaques. To elucidate fur ther the role of this protein in the degenerative process, a quantitat ive study of its distribution in the cerebral cortex of non-demented a nd AD patients, all older than 85 years of age, was performed using im munocytochemistry. Using a stereological approach, we found that in co rtical areas affected in AD, such as the entorhinal, inferior temporal and superior frontal cortices, the percentage of NFT-free neurons dis playing clusterin immunoreactivity was significantly higher than that in non-demented cases. No such increase in the density of clusterin-im munoreactive neurons was seen in cortical areas that were less affecte d in the disease process. Furthermore, clusterin immunoreactivity was rarely observed in NFT-containing neurons. In conjunction with previou s observations in peripheral tissues, these data suggest that clusteri n may have a neuroprotective role, and that in AD, low cellular expres sion of this protein may be associated with neuronal degeneration and death.