AMYGDALA IN ALZHEIMER'S DISEASE AND NORMAL AGING

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The overall goal of this research proposal is to elucidate morphologic relations and alterations of neurons in human amygdala obtained at autopsy from normal aged individuals and those afflicted with Alzheimer's disease (AD). The amygdala occupies a strategic position in the circuitry of the limbic system, maintaining connections between cortical association areas and visceral-associated nuclei located subcortically, and undergoes severe pathologic alterations in AD. The first aim is to determine whether pathological alterations resulting from AD have predilection for specific amygdaloid nuclei. Initial morphometric analyses seek to determine whether amygdaloid atrophy in AD correlates with decreased neuronal-packing density, reduced neuronal size or neuron loss. The topographic distribution of neuritic plaques (NPs) and neurofibrillary tangles (NFTs) will be mapped using thioflavin S to test the hypothesis that certain amygdaloid nuclei are selectively vulnerable in AD. Amygdaloid nuclei with severe, intermediate and negligible levels of pathology will be selectively studied at the ultrastructural level to ascertain synaptic relations between normal and pathologically altered structures, and to determine whether alterations in synaptic length and synaptic density correlate with AD. The second aim is to determine the relationship between NFTs in cortical and amygdaloid projection neurons, and NPs in several of their respective terminal fields. Data from morphometric analyses of temporal cortical areas, including hippocampal formation and subcortical nuclei connectionally related to the amygdala will be used to test for a transneuronal effect in the pathogenesis of AD. The third aim entails using experimental neuroanatomical techniques to determine the relationships between intrinsic neurons and AD pathology in chemically defined populations of amygdaloid neurons. The structural substrate of intrinsic neurons and their synaptic relations will be analyzed with light and electron microscopy using NADPH histochemistry and antisera against somatostatin (SOM) and neuropeptide tyrosine (NPY). The results of this research are relevant to a wide range of basic and clinical neuroscience research. The amygdala figures prominently in limbic circuitry and interruptions of this circuitry cause debilitating deficits in memory, attention and affect. Results of these studies will provide qualitative and quantitative information fundamental to understanding structure-function relationships at the synaptic level in normal aged individuals, as well as in neurological disorders such as epilepsy, Alzheimer's and Parkinson's diseases.