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Role of the Low-density Lipoprotein Receptor–Related Protein in -Amyloid Metabolism and Alzheimer Disease

Bradley T. Hyman, MD, PhD; Dudley Strickland, PhD; G. William Rebeck, PhD

Arch Neurol. 2000;57:646-650.

Deposition of -amyloid (A), a metabolite of approximately 4 kd of the amyloid precursor protein, is a critical pathological feature in Alzheimer disease. We postulate that deposition reflects an imbalance of A synthesis and clearance. Several pathways that impact A converge on a single receptor molecule, the low-density lipoprotein receptor–related protein (LRP). This multifunctional receptor is the major neuronal receptor both for apolipoprotein E (apoE, protein; APOE, gene) and for ₂-macroglobulin (₂M, protein; A2M, gene), and it mediates clearance of apoE/A and ₂M/A complexes. The LRP also interacts with the amyloid precursor protein itself. In this review, we highlight data that support a role for LRP in A metabolism and hypothesize that LRP therefore plays a critical role in Alzheimer disease.

From the Alzheimer Disease Research Laboratory, Massachusetts General Hospital, Boston (Drs Hyman and Rebeck), and The Holland Laboratory, American Red Cross, Rockville, Md (Dr Strickland).

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