Using plasma samples from participants in the neuroimaging sub-study of the Baltimore Longitudinal Study of Aging (BLSA), we have identified a robust peripheral signature associated with brain amyloid deposition. Several of these plasma proteins, including apolipoprotein-E (ApoE) have established roles in amyloid clearance pathways. In another approach, we first used proteomic analyses of plasma to demonstrate that the concentration of clusterin (also known as apolipoprotein-J/ApoJ) is associated with atrophy of the entorhinal cortex as well as with faster cognitive decline in patients with established Alzheimer’s disease (AD). We then tested whether plasma clusterin concentration was also associated with extent of brain amyloid deposition in normal aging. Using a commercially available ELISA assay, we showed that clusterin, measured in plasma samples collected 10 years prior to the 11C-PiB PET scans, is associated with greater amyloid deposition within the medial temporal lobe.

Taken together with recent genome wide association studies demonstrating that polymorphic variation in the clusterin gene is associated with a risk of AD, these results suggest a key role of this amyloid chaperone protein in AD pathogenesis. Our strategy combining 11C-PiB PET imaging of the brain with proteomic analyses of plasma holds promise for the discovery of biologically relevant peripheral biomarkers for AD.

Acknowledgement: This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging.