Identification of a beta-amyloid-binding plasma protein, LRP1: implications for biomarker research and therapy in Alzheimer's disease.
Evaluation of Sagare A, Deane R, Bell RD et al.: Clearance of amyloid-beta by circulating lipoprotein receptors. Nat. Med. (2007) (Epub ahead of print) [1] . Sagare and coworkers have identified a major amyloid-beta (Abeta)-binding protein in plasma low-density lipoprotein receptor-related protein-1 (LRP1). This protein may bind 70-90% of the Abeta that circulates in peripheral blood and seems to function as a peripheral sink for Alzheimer's disease (AD) causing brain Abeta. Using a mouse model of AD, the authors demonstrate that boosting the capacity of the sink by administering a recombinant form of soluble LRP1 (sLRP1) reduces brain amyloid plaque load and improves learning and memory. They extend these results by demonstrating that patients with AD have depressed plasma sLRP1 levels. Their data suggest that exogenously administered, recombinant sLRP1 may provide a novel approach to reduce or reverse the AD-related build up of Abeta in the brain. Furthermore, it would be interesting to explore the possibility that reduced sLRP1 levels in plasma may be a specific biochemical sign of incipient AD.
Zetterberg
Henrik
H
Göteborg University, Institute of Neuroscience & Physiology, Department of Psychiatry & Neurochemistry, The Sahlgrenska Academy, S-431 80 Mölndal, Sweden. henrik.zetterberg@gu.se