title: Non-A beta component of Alzheimer's disease amyloid (NAC) is amyloidogenic.
abstract: The non-A beta component of Alzheimer's disease (AD) amyloid (NAC) was identified biochemically as the second major component in the amyloid purified from brain tissue of AD patients. NAC, derived from its 140 amino acid long precursor, NACP, is at least 35 amino acids long (NAC35) although its amino terminus is not definitely determined. An antiserum, anti-NAC-X1, was raised against the amino-terminal 9 amino acid sequence of NAC35 and purified on a peptide affinity column. This affinity-purified anti-NAC-X1 antibody immunostained amyloid in AD brain sections and recognized NAC35 but not NACP on Western or dot blot. In aqueous solutions, synthetic NAC35 self-aggregated in a time-, concentration-, and temperature-dependent manner. NAC35 was detected initially as a monomer with a molecular mass of 3500 Da but became aggregated as a function of time into a higher molecular mass component that could not migrate into the gel. The aggregate of NAC35 showed green-gold birefringence after Congo red staining when analyzed under polarized light and fiber-like structure when analyzed ultrastructurally. These results suggest that NAC can form amyloid after it has been cleaved out of its precursor and may be a crucial factor in amyloidosis in the AD brain.
authors.affiliation: Department of Neurosciences, School of Medicine, University of California at San Diego, La Jolla 92093-0624, USA.
authors.forename: A
authors.initials: A
authors.lastname: Iwai
authors.forename: M
authors.initials: M
authors.lastname: Yoshimoto
authors.forename: E
authors.initials: E
authors.lastname: Masliah
authors.forename: T
authors.initials: T
authors.lastname: Saitoh
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D003224:Congo Red; D006801:Humans; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary
chemical_list: D000682:Amyloid; D003224:Congo Red