Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels.
The protein component of Alzheimer's disease amyloid [neurofibrillary tangles (NFT), amyloid plaque core and congophilic angiopathy] is an aggregated polypeptide with a subunit mass of 4 kd (the A4 monomer). Based on the degree of N-terminal heterogeneity, the amyloid is first deposited in the neuron, and later in the extracellular space. Using antisera raised against synthetic peptides, we show that the N terminus of A4 (residues 1-11) contains an epitope for neurofibrillary tangles, and the inner region of the molecule (residues 11-23) contains an epitope for plaque cores and vascular amyloid. The non-protein component of the amyloid (aluminum silicate) may form the basis for the deposition or amplification (possible self-replication) of the aggregated amyloid protein. The amyloid of Alzheimer's disease is similar in subunit size, composition but not sequence to the scrapie-associated fibril and its constituent polypeptides. The sequence and composition of NFT are not homologous to those of any of the known components of normal neurofilaments.
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000596:Amino Acids / Q000032:analysis; D000682:Amyloid / Q000032:analysis*; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D006801:Humans; D007118:Immunoassay; D008062:Lipofuscin / Q000302:isolation & purification; D046911:Macromolecular Substances; D008970:Molecular Weight; D009454:Neurofibrils / Q000032:analysis*
D000596:Amino Acids; D000682:Amyloid; D008062:Lipofuscin; D046911:Macromolecular Substances