Activity of Hippocampal CA1 Neurons in Alzheimer's Disease is not Affected by the Presence of Adjacent Neuritic Plaques

Alzheimer's disease (AD) is neuropathologically characterized by neuritic plaques (NPs) and neurofibrillary tangles and functionally by a decreased metabolic rate of neurons. Our previous studies showed that in brain areas which are extensively affected by plaques and tangles, i.e. the CA1 area of the hippocampus and the hypothalamic tuberomamillary nucleus, neuronal protein synthetic ability is significantly lower in AD patients than in controls. However, the presence of tangles as shown by Bodian staining appeared not to be directly related to decreased protein synthetic ability of neurons. In order to study to what extent the metabolic function of neurons might be affected by the other neuropathological hallmark of AD, i.e. NPs, which are presumed to contain neurotoxic compounds, we studied eight severely demented AD patients matched for the ApoE genotype (ApoE 3/3). Using an image analysis system, the size of the neuronal Golgi apparatus (GA) and of the cell profile area was measured as a parameter for protein synthetic activity in the CA1 area of these patients. NPs were stained by Bodian, and subsequently the distance of each neuron with an immunostained GA to the nearest NP was measured. Our results showed that neither NP density nor the distance between NPs and neurons correlated with the protein synthetic ability of neurons as judged by the size of the GA. Based on these results we suggest that in AD the presence of NPs and decreased neuronal protein synthetic ability are basically two independent phenomena