Changes in synaptic expression of clathrin assembly protein AP180 in Alzheimer's disease analysed by immunohistochemistry

Clathrin assembly protein AP180 plays a regulatory role in clathrin-mediate d synaptic vesicle recycling in synapses. Previously, using immunoblot anal ysis, we observed a significant reduction of AP180 protein in Alzheimer's d isease neocortex. in this study, we examined immunohistochemically the expr ession of AP180 in post mortem brains with Alzheimer's disease (n = 5) in c omparison with neurologically normal controls (n = 5). Overall, AP180 was r evealed as immunoreactive punctate granules located in the neuropil, and ar ound neuronal cell bodies and their processes, consistent with the typical expression of synaptic proteins. Reduced density of AP180 immunoreactive pu ncta was seen throughout all layers of the superior frontal gyrus in Alzhei mer's disease, but the loss of AP180 immunoreactivity was not as prominent in the cerebellum. This regional difference is in agreement with our previo us results from immunoblot analyses. In the hippocampus, cell body AP180 im munoreactivity normally seen in the hilus and the CA3 regions of control br ains was completely lost in Alzheimer's disease. In addition, AP180 immunor eactivity in the molecular layer of the dentate gyrus showed several change s in Alzheimer's disease. These appeared to be expansion of the inner molec ular layer and relative changes in immunoreactivity that resulted in cleare r delineation of the inner and outer molecular layers. These results provide anatomical and spatial information on AP180 expressio n in Alzheimer's disease brains. The variations in altered AP 180 immunorea ctivity in different brain regions of Alzheimer's disease may underlie the dysfunction of the corresponding synapses. (C) 1999 IBRO. Published by Else vier Science Ltd.