Rapid Detection of a Pentanucleotide Deletion Polymorphism in the Human α2-Macroglobulin Gene

Alpha-2 macroglobulin (α2M) is a serum glycoprotein and a panproteinase inhibitor found in various tissues, including plasma and cerebrospinal fluid. α2M is thought to inactivate proteinases by a specific trapping mechanism in the so-called “bait” region of the protein (1). α2M is also a ligand for the LDL receptor-related protein, and both are up-regulated after brain injury and in regions of the brain affected by Alzheimer disease. Additionally, α2M binds to the amyloid β peptide (2)(3), which leads to attenuation of both fibrillogenesis and neurotoxicity (4) and which is cleared by the LDL receptor-related protein. Recently, a pentanucleotide deletion in the 5′ splice site of exon 18, which encodes a portion of the α2M bait region, has been suggested to be genetically associated with an increased risk for developing Alzheimer disease (5). α2 …