Perisomatic granules (non-plaque dystrophic dendrites) of hippocampal CA1 neurons in Alzheimer's disease and Pick's disease: a lesion distinct from granulovacuolar degeneration

A number of pathological changes have been reported in relation to CA1 pyra midal cells in Alzheimer's disease (AD), among them hyperphosphorylation of tau protein followed by the formation of filamentous tau lesions, granulov acuolar degeneration (GVD), Hirano bodies and spindle-shaped dilatations of distal apical dendrites. Juxtacellular clusters of glutamate receptor (Glu R)-positive granules around pyramidal cells of the CA1 sector have been rec ently reported under the term "non-plaque dystrophic dendrites". We indepen dently found that CA1 pyramidal cells in AD patients are regularly surround ed by ubiquitin-positive granules measuring 1-4 mum in diameter, which we h ave termed perisomatic granules (PSG). Using confocal microscopy, ubiquitin - and GluR-reactive granules were found to largely coincide and to correspo nd to the same structure. By immunoelectron microscopy PSG were found to co nsist of GluR1-2-reactive enlarged synaptic boutons containing tubulo-filam entous or floccular material. PSG were found to be consistently associated with pyramidal (principal) cells but not with interneurons of the CA1 secto r. Dual-labeling experiments have shown that PSG are preferentially associa ted with tau-immunoreactive "pretangle" neurons but not with cells containi ng filamentous tau inclusions or with tau-negative nerve cell bodies. The n umber of PSG was found to increase with the severity of AD changes with alm ost no PSG found in Braak stages I and II and few in stage III. Furthermore , PSG were not AD specific, as shown by their presence around CA1 pyramidal cells in Pick's disease. The reasons for GluR reactivity and ubiquitin com plex formation in enlarged perisomatic boutons are unclear. Marked changes in GluR subunits have been observed in association with even moderate AD pa thology in hippocampal pyramidal cells in AD and our findings suggest a pat hogenic link between PSG and early tau pathology in CA1 neurons. PSG might represent residual and abnormally clustered GluR subunits in degenerating p erisomatic neurites. Our work confirms and extend previous study on perisom atic "non-plaque dystrophic dendrites" in AD and establish PSG as a patholo gical entity distinct from GVD. In addition PSG should be acknowledged amon g main histological changes associated with hippocampal neurons in AD and P ick's disease.