Synthetic peptide homologous to. beta. protein from Alzheimer's disease forms amyloid-like fibrils in vitro

Journal Article · Thu Oct 01 00:00:00 EDT 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.19.6953· OSTI ID:7131292

Kirschner, D A; Inouye, H; Duffy, L K; Sinclair, A; Lind, M; Selkoe, D J

Progressive amyloid deposition in senile plaques and cortical blood vessels may play a central role in the pathogenesis of Alzheimer's disease. The authors have used x-ray diffraction and electron microscopy to study the molecular organization and morphology of macromolecular assemblies formed by three synthetic peptides homologous to ..beta.. protein of brain amyloid: ..beta..-(1-28), residues 1-28 of the ..beta.. protein; (Ala/sup 1 -/..beta..-(1-28), ..beta..-(1-28) with alanine substituted for lysine at position 16; and ..beta..-(18-28), residues 18-28 of the ..beta.. protein. ..beta..-(1-28) readily formed fibrils in vitro that were similar in ultrastructure to the in vivo amyloid and aggregated into large bundles resembling those of senile plaque cores. X-ray patterns from partially dried, oriented pellets showed a cross-..beta..-conformation. (Ala/sup 16/)..beta..-(1-28) formed ..beta..-pleated sheet assemblies that were dissimilar to in vivo fibrils. The width of the 10-A spacing indicated stacks of about six sheets. Thus, substitution of the uncharged alanine for the positively charged lysine in the ..beta..-strand region enhances the packing of the sheets and dramatically alters the type of macromolecular aggregate formed. BETA-(18-28) formed assemblies that had even a greater number of stacked sheets. The findings on these homologous synthetic assemblies help to define the specific sequence that is required to form Alzheimer's-type amyloid fibrils, thus providing an in vitro model of age-related cerebral amyloidogenesis.

• Research Organization: Children's Hospital, Boston, MA (USA)
• OSTI ID: 7131292
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:19
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
NERVOUS SYSTEM DISEASES
PATHOGENESIS
PROTEINS
CONFORMATIONAL CHANGES
X-RAY DIFFRACTION
ALANINES
HISTOLOGY
LYSINE
PATIENTS
PEPTIDES
STRUCTURAL MODELS
TRANSMISSION ELECTRON MICROSCOPY
AMINO ACIDS
CARBOXYLIC ACIDS
COHERENT SCATTERING
DIFFRACTION
DISEASES
ELECTRON MICROSCOPY
MICROSCOPY
ORGANIC ACIDS
ORGANIC COMPOUNDS
SCATTERING
550602* - Medicine- External Radiation in Diagnostics- (1980-)