Diminished neuronal metabolic activity in Alzheimer's disease

An increasing number of studies have appeared in the literature suggesting that Alzheimer's disease (AD) is a hypometabolic brain disorder. Decreased metabolism in AD has been revealed by a variety of in vivo and postmortem m ethods and techniques including positron emission tomography and glucose me tabolism. We used the: size of the Golgi apparatus (GA) and cell profile ar ea as indicators of neuronal activity in postmortem material. Using an anti body against MG-160, a sialoglycoprotein of the medial cisternae of the GA, we were able to visualize ansi quantify the GA area. In a series of experi ments, we tried to relate neuronal metabolism to different hallmarks of AD, i.e. plaques and tangles, and also to genetic risk factors for AD like age and (apolipoprotein E) ApoE polymorphism. Our results showed that in AD th ere is indeed a clear reduction in brain metabolism in several severely aff ected brain regions including the nucleus basalis of Meynert (NBM), the CA1 area of the hippocampus and the hyplothalamic tuberomamillary nucleus. How ever, the reduction in neuronal activity did not seem to be caused by the p resence of neuropathological hallmarks of AD, i.e. plaques and tangles. The re was, however, a clear relationship between the presence of ApoE epsilon 4 alleles and a decrease in GA size. Our data suggest that decreased neuron al activity and neuropathological hallmarks of AD, such as plaques and tang les, are basically independent phenomena. Moreover, ApoE epsilon 4 may part icipate in the pathogenesis of AID by decreasing neuronal metabolism. The m ain implication of these findings is that therapeutic strategies in AD shou ld be focussed on reactivation of neuronal metabolism.