Plasma Protein Linked to Development and Severity of Alzheimer's

Higher concentrations of clusterin, a protein in the blood plasma, have shown to be linked to the development, severity and progression of Alzheimer’s disease, according to a study published in the Archives of General Psychiatry.

Numerous studies have indicated that levels of certain metabolites and proteins in the plasma might signify responses to brain changes in Alzheimer’s disease (AD), but none have been replicated. With that in mind, Madhav Thambisetty, M.D., Ph.D., of Institute of Psychiatry, King’s College London, and colleagues utilized a combined proteomic and neuroimaging approach to identify plasma proteins associated with correlates of Alzheimer’s disease pathology.

Participants in both a multicenter European study (AddNeuroMed) and the Baltimore Longitudinal Study of Aging—some of whom had Alzheimer’s, some with mild cognitive impairment, and some who were healthy controls—underwent standardized clinical assessments and neuroimaging. In addition, their blood plasma was examined for proteins that may be associated with Alzheimer’s.

They found that clusterin “was associated with atrophy of the entorhinal cortex, baseline disease severity, and rapid clinical progression” in Alzheimer’s, and that “increased plasma concentration of clusterin was predictive of greater fibrillar amyloid-β burden in the medial temporal lobe.” Although patients with Alzheimer’s had increased clusterin messenger RNA in blood, “there was no effect of single-nucleotide polymorphisms in the gene encoding clusterin with gene or protein expression.”

Thambisetty and colleagues believe that the results of the study “demonstrate an important role of clusterin in the pathogenesis of AD and suggest that alterations in amyloid chaperone proteins may be a biologically relevant peripheral signature of AD.”