Myelin Basic Protein Binds to and Inhibits the Fibrillar Assembly of Aβ42 in Vitro

The deposition of amyloid β-protein (Aβ) fibrils into plaques within the brain parenchyma and along cerebral blood vessels is a hallmark of Alzheimer’s disease. Aβ peptides are produced through the successive cleavage of the Aβ precursor protein by β- and γ-secretase, producing peptides between 39 and 43 amino acids in length. The most common of these are Aβ40 (the most abundant) and Aβ42. Aβ42 is more fibrillogenic than Aβ40 and has been implicated in early Aβ plaque deposition. Our previous studies determined that myelin basic protein (MBP) was capable of inhibiting fibril formation of a highly fibrillogenic Aβ peptide containing both E22Q (Dutch) and D23N (Iowa) mutations associated with familial forms of cerebral amyloid angiopathy [Hoos, M. D., et al. (2007) J. Biol. Chem. 282, 9952−9961]. In this study, we show through a combination of biochemical and ultrastructural techniques that MBP is also capable of inhibiting the β-sheet fibrillar assembly of the normal Aβ42 peptide. These findings suggest th...