Identification of a β-Amyloid-Binding Plasma Protein, LRP1: Implications for Biomarker Research and Therapy in Alzheimer‘s Disease

Abstract

Evaluation of Sagare A, Deane R, Bell RD et al.: Clearance of amyloid-β by circulating lipoprotein receptors. Nat. Med. (2007) (Epub ahead of print) [1]. Sagare and coworkers have identified a major amyloid-β (Aβ)-binding protein in plasma low-density lipoprotein receptor-related protein-1 (LRP1). This protein may bind 70–90% of the Aβ that circulates in peripheral blood and seems to function as a peripheral sink for Alzheimer‘s disease (AD) causing brain Aβ. 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 Aβ 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.

Keywords: :

• amyloid-β
• Alzheimer’s disease
• biomarker
• pathogenesis
• plasma

Financial & competing interests disclosure

Work in the author‘s group is supported by the Swedish Research Council, the Swedish Council for Working Life and Social Research, the EU project cNEUPRO and the Alzheimer Foundation. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Work in the author‘s group is supported by the Swedish Research Council, the Swedish Council for Working Life and Social Research, the EU project cNEUPRO and the Alzheimer Foundation. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.