Biophysical characterization of longer forms of amyloid beta peptides: possible contribution to flocculent plaque formation.
Alzheimer's disease is characterized by amyloid deposits in the parenchyma and vasculature of the brain. The plaques are mainly composed of amyloid beta (Abeta) peptides ending in residues 40 and 42. Novel longer Abeta peptides were found in brain homogenates of mouse models of Alzheimer's disease and human brain tissue of patients carrying the familial amyloid precursor protein V717F mutation. The biophysical characteristics of these longer Abeta peptides and their role in plaque formation are not understood. We chose to focus our studies on Abeta peptides ending in residues Ile45, Val46 and Ile47 as these peptides were identified in human brain tissue. A combination of circular dichroism and electron microscopy was used to characterize the secondary and tertiary structures of these peptides. All three longer Abeta peptides consisted mainly of a beta-sheet secondary structure. Electron microscopy demonstrated that these beta-structured peptides formed predominantly amorphous aggregates, which convert to amyloid fibres over extended time periods. As these longer peptides may act as seeds for the nucleation of fibrils composed predominantly of shorter amyloid peptides, these interactions were studied. All peptides accelerated the random to beta-structural transitions and fibril formation of Abeta40 and 42.
Lambermon
Mark H L
MH
Centre for Research in Neurodegenerative Diseases and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Rappaport
Rebecca V
RV
McLaurin
JoAnne
J
D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D000818:Animals; D002942:Circular Dichroism; D008854:Microscopy, Electron; D009412:Nerve Fibers / Q000187:drug effects / Q000648:ultrastructure; D016716:PC12 Cells; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry; D058225:Plaque, Amyloid / Q000737:chemistry*; D051381:Rats; D014443:Tyrosine / Q000378:metabolism
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D014443:Tyrosine