THE CELLULAR PATHOLOGY ASSOCIATED WITH ALZHEIMER BETA-AMYLOID DEPOSITS IN NONDEMENTED AGED INDIVIDUALS

In this study, we have compared the cellular pathology associated with beta-amyloid (betaA) deposits which characterize Alzheimer's disease (AD) in demented patients with pathologically confirmed AD, with that in non-demented aged individuals. Brain sections from two severely demented AD cases, six non-demented individuals with betaA deposits, and six age-matched controls devoid of betaA deposits were double-immunostained with antibodies against betaA, and antibody markers for neurofibrillary tangles (NFT), astrocytes and microglial cells. We found that the severely demented patients displayed numerous plaques of variable morphology, most of which were associated with NFT, hypertrophied astrocytes and reactive microglial cells. In contrast, non-demented patients showed fewer plaques, few or no NFT and less astroglial and microglial reaction. The number of plaques with associated abnormal cellular elements were much lower in non-demented than in demented cases. Furthermore, classical plaques were more likely to be associated with abnormal cellular elements than diffuse plaques, which were most often devoid of any associated cellular change. These findings suggest that: (i) betaA plaques in non-demented individuals may represent an early stage of AD; (ii) betaA deposition is the first recognizable pathological abnormality of AD; and (iii) NFT, and astro- and microglial proliferation are later features, possibly secondary to the known dystrophic effects of the betaA peptide and other fragments of its precursor protein.