Blood Protein Reflects Severity and Progression in Alzheimer's

Clusterin identified as a 'peripheral signature' of Alzheimer's but not a stand-alone biomarker

09 july 2010-- Elevated plasma concentration of clusterin is associated with Alzheimer's disease pathology, severity, and rate of clinical progression, according to research published in the July issue of the Archives of General Psychiatry.

Madhav Thambisetty, M.D., of King's College London, and colleagues, using data on subjects from two studies of Alzheimer's disease, compared blood samples from subjects with the disease, subjects with mild cognitive impairment, and healthy subjects to identify associations of blood proteins with brain atrophy, disease severity, and clinical progression rate. In an extension study in six-month-old transgenic mice modeling Alzheimer's disease, the researchers also looked for associations between candidate proteins and brain amyloid.

The researchers found that clusterin/apolipoprotein J was associated with disease severity at baseline, entorhinal cortex atrophy, and rapid disease progression. Among subjects with Alzheimer's disease, increased clusterin messenger RNA in the blood also was observed. A greater concentration of clusterin in blood was associated with a greater burden of amyloid-β in the medial temporal lobe. In the mouse model, the researchers found increased blood clusterin, age-related increased brain clusterin, and amyloid and clusterin together in brain plaques.

"We identified clusterin as a plasma protein associated with disease pathology, severity, and progression in Alzheimer's disease. Although these findings do not support the clinical utility of plasma clusterin concentration as a stand-alone biomarker for Alzheimer's disease, they reveal a robust peripheral signature of this amyloid chaperone protein that is responsive to key features of disease pathology," the authors write.

Kings College London has registered as intellectual property a process for the use of plasma proteins, including clusterin, as Alzheimer's disease biomarkers, with two of the study authors named as inventors. Another study author disclosed receiving research support from pharmaceutical and medical device companies.

Abstract
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