2 DISTINCT UBIQUITIN IMMUNOREACTIVE SENILE PLAQUES IN ALZHEIMERS-DISEASE - RELATIONSHIP WITH THE INTELLECTUAL STATUS IN 29 CASES

The aim of this study was the analysis of the development of neurofibrillary tangles (NFT) and senile plaques (SP) during aging and senile dementia of the Alzheimer type. The lesions stained by ubiquitin, tau and betaA4 antibodies were studied in Brodmann's area 22 (superior temporal gyrus) in 29 cases. Samples were from a group of women over 75 years of age, psychometrically assessed and either normal or affected by Alzheimer's disease at various degrees of severity. NFT were less numerous when revealed by ubiquitin than by tau antibodies, suggesting that ubiquitin immunoreactivity appeared later in the course of the disease. Ubiquitin immunoreactive (IR) SP were made of clusters of IR neurites usually organized around a central amyloid core. Two types of ubiquitin-IR SP were designated. ''Globular neurite SP'' contained weakly immunostained globular neurites. They were densest in the least affected cases. However, they were not seen in every normal or lightly affected case, and were always present in the most affected ones. The density of these globular neurite SP was not significantly correlated with the severity of dementia, nor with the density of the lesions stained by tau antibodies (neuritic component of SP, NFT and neuropil threads) or by betaA4 antibodies (diffuse or dense deposits). The ''curly neurite'' type of SP contained curly neurites strongly immunostained by ubiquitin antibodies. They exhibited the highest density in the most affected cases, where they were always present. They were lacking in the least affected cases. They were always found together with the globular neurite SP. The density of these curly neurite SP was significantly correlated with the severity of dementia, and with the density of tau-IR lesions and dense amyloid betaA4 deposits. It was not correlated, however, with the density of diffuse betaA4 deposits. Our results suggest that the globular neurite SP and the curly neurite SP were not systematically linked. Ubiquitin immunoreactivity in the globular neurite SP could be a transient event in the course of the disease and in the formation of SP. On the contrary, ubiquitin immunoreactivity in the curly neurite SP and NFT seemed to appear after tau immunoreactivity. These ubiquitin conjugates could constitute an irreversible lesion related to dementia.