Clusterin and amyloid may be linked in Alzheimer’s brain atrophy

The usual subjects in the Alzheimer’s brain are patterns of beta-amyloid plaque and tau aggregation, but a third perpetrator, clusterin, may be playing a more important role in the development of the disease than previously thought, according to a study published Dec. 30 in JAMA Neurology.

Rahul S. Desikan, MD, PhD, from the department of radiology at the University of California, San Diego, La Jolla, and colleagues evaluated the role elevated clusterin glycoprotein in the brain plays in the deposition of amyloid and associated brain atrophy in both subjects with mild cognitive impairment and healthy controls. Formerly researchers did not have a good grip on whether the presence of clusterin was a protective or detrimental factor in early Alzheimer’s disease development. Results showed that elevated clusterin levels in cerebral spinal fluid were correlated with increased amyloid plaque in an area of the brain thought to be the point of origin for Alzheimer’s. No such connection was found between clusterin and tau fibril development.

“Here, we showed that in nondemented older individuals, beta-amyloid associated entorhinal cortex atrophy occurs in the presence of elevated clusterin,” wrote Desikan et al. “We also found that the effect of clusterin on beta-amyloid associated entorhinal cortex atrophy is not confounded or explained by p-tau. Taken together, this implicates a potentially important role for clusterin in the earliest stages of the Alzheimer neurodegenerative process and suggests independent effects of clusterin and tau on beta-amyloid associated volume loss.”

For this study, a total 241 dementia-free subjects were evaluated for mild cognitive decline, given lumbar puncture and MRI scan. Researchers were able to conclude that cerebrospinal fluid clusterin was positively linked with brain atrophy of patients with entorhinal cortex beta-amyloid, but not those who tested negative.

“These findings provide novel insights into the preclinical stage of Alzheimer’s disease,” the authors wrote. “Although prior research suggests that clusterin by itself may not represent a marker of presymptomatic Alzheimer’s disease, our work indicated that the presence of clusterin may represent a critical link between beta amyloid deposition and entorhinal cortex degeneration in preclinical AD.”