Stereochemical specificity of Alzheimer's disease β-peptide assembly

✍ Scribed by William P. Esler; Evelyn R. Stimson; Jordan B. Fishman; Joseph R. Ghilardi; Harry V. Vinters; Patrick W. Mantyh; John E. Maggio

• Publisher: Wiley (John Wiley & Sons)
• Year: 1999
• Tongue: English
• Weight: 267 KB
• Volume: 49
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/(sici)1097-0282(199905)49:6<505::aid-bip8>3.0.co;2-i

✦ Synopsis

The formation and growth of insoluble amyloid deposits composed primarily of the human ␤-amyloid peptide (A␤) in brain is an essentially invariant feature of Alzheimer's disease (AD) and is widely believed to contribute to the progressive neurodegeneration of the disorder. To probe the specificity of amyloid formation and growth, we synthesized and examined the selfassembly of D-and L-stereoisomers of A␤ in vitro. While both enantiomers formed insoluble aggregates at similar rates with amyloid-like fibrillar morphology, deposition of soluble A␤ peptide onto preexisting A␤ aggregates was stereospecific. Although the L-peptide deposited readily onto immobilized L-A␤ aggregates with first-order kinetic dependence on soluble peptide concentration, essentially no association between the D-peptide and L-template was observed. Similarly, the D-peptide deposited with first-order kinetics onto a D-A␤ aggregate template but did not deposit onto