Neuronal origin of cerebral amyloidogenic proteins: their role in Alzheimer's disease and unconventional virus diseases of the nervous system.

Abstract

The protein component of Alzheimer's disease amyloid (neurofibrillary tangles, amyloid plaque cores and congophilic angiopathy) is an aggregated polypeptide with a subunit mass of approximately 4 kDa (the A4 monomer). The aggregational properties of this monomer may explain the amyloidogenic nature of the protein: the native monomer forms dimers, tetramers and higher oligomeric species which are dependent on pH, ionic strength and concentration; the synthetic peptide corresponding to residues 1-28 spontaneously forms fibrils in vitro. Based on the degree of N-terminal heterogeneity, the A4 monomer aggregates first in neurons and later in the extracellular space. Using antisera raised against..