Conservation of Brain Amyloid Proteins in Aged Mammals and Humans with Alzheimer's Disease

Abstract

The formation of clusters of altered axons and dendrites surrounding extracellular deposits of amyloid filaments (neuritic plaques) is a major feature of the human brain in both aging and Alzheimer's disease. A panel of antibodies against amyloid filaments and their constituent proteins from humans with Alzheimer's disease cross-reacted with neuritic plaque and cerebrovascular amyloid deposits in five other species of aged mammals, including monkey, orangutan, polar bear, and dog. Antibodies to a 28-amino acid peptide representing the partial protein sequence of the human amyloid filaments recognized the cortical and microvascular amyloid of all of the aged mammals examined. Plaque amyloid, plaque neurites, and neuronal cell bodies in the aged animals showed no reaction with antibodies to human paired helical filaments. Thus, with age, the amyloid proteins associated with progressive cortical degeneration in Alzheimer's disease are also deposited in the brains of other mammals. Aged primates can provide biochemically relevant models for principal features of Alzheimer's disease: cerebrovascular amyloidosis and neuritic plaque formation.