M. Kidd

Monoclonal antibodies raised against a subsequence of senile plaque core protein react with plaque cores, plaque periphery and cerebrovascular amyloid in Alzheimer's disease

Four monoclonal antibodies (1D2/1/2, 1G10/2/3, 3B6/1/1, 4D12/2/6) were raised against a synthetic peptide consisting of residues 8-17 of a protein reported to be common to senile plaque cores, cerebrovascular amyloid and neurofibrillary tangles in Alzheimers disease. In an immunoperoxidase study of Alzheimer brain tissue, these antibodies stained plaque and vascular amyloid but not tangles, suggesting that the polypeptide chain in the region of residues 8-17 is exposed in the former two but, if present, inaccessible in the latter. In addition, staining of granular material in the plaque periphery was observed. These antibodies will be useful tools for future work on the origin of this protein.

CNS amyloid proteins in neurodegenerative diseases

The amyloid plaques found in neurodegenerative diseases show considerable morphologic diversity. Two amyloidogenic proteins have been isolated from the brains of humans and animals with neurodegenerative diseases-β-protein from Alzheimers disease (AD) and Downs syndrome, and prion protein (PrP) from scrapie and Creutzfeldt-Jakob disease (CJD). Using monoclonal antibodies to a synthetic peptide corresponding to a portion of β-protein and rabbit antiserum to hamster scrapie PrP 27–30, we examined in situ amyloid plaques on sections from cases of neurodegenerative diseases, including cases with a spectrum of plaque types. Anti-β-peptide stained cerebrovascular and plaque core amyloid in all AD cases as well as cerebrovascular amyloid and senile plaque core amyloid in five elderly CJD cases. Anti-PrP stained plaques in CJD, kuru, and Gerstmann-Sträussler syndrome cases but not cerebrovascular amyloid or plaques in AD. Dual localization experiments showed that in cases with a mixture of plaque types, the antibodies identified different populations of plaques that showed anatomic heterogeneity. Colocalization of the two proteins was not observed in any plaque type. The data suggest that in neurodegenerative diseases two major plaque types exist, which have different etiologic origins. Our results emphasize the need for classification of CNS amyloids based not on their morphology but on the macromolecular components comprising these pathologic polymers.