RESUMO
The occurrence of senile plaques consisting of amyloid-ß protein (Aß) is a major neuropathological hallmark of Alzheimer's disease (AD). We previously developed and characterized monoclonal antibodies 31-2 and 75-2 that specifically bind to nonfibrillar Aß1-42 aggregates with diameters of more than 220 and 50 nm, respectively. Here, we report the use of these antibodies to examine the aggregation of exogenous Aß1-42 in cultured rat hippocampal neurons. From 6 to 24 h after transfection of Aß1-42, antibody 75-2 immunolabeled almost all transfected neurons, whereas 31-2-positive cells were restricted to a part of the transfected neurons and gradually increased in number. Expression of the F19S/L34P-mutant Aß1-42, which showed less of a tendency to aggregate, resulted in clearly reduced immunoreactivity to both antibodies. We also immunohistochemically investigated the temporal cortices of patients with AD and found that 31-2 preferentially labeled the cores of a subpopulation of large amyloid plaques. The relative number of 31-2-immunoreactive plaques was found to correlate with the Braak stages of neurofibrillary tangles, but not with that of amyloid plaques. These results suggest that 31-2-reactive Aß aggregates develop with a delayed time course in cultured neurons and amyloid plaques of AD brains.
