MESOCORTICAL ANATOMY AND PLASTICITY

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A continuing plan is outlined that has the dual purpose of investigating cortical neural systems that arise from the limbic lobe in the nonhuman primate and the pathological alteration of their probable homologues as seen in Alzheimer's disease. The limbic, or mesocortices, form a major part of the medial surface of the primate brain and include such areas as the cingulate cortex, parahippocampal cortex, posterior orbitofrontal cortex and the cortex of the temporal pole. The central goal of the principal investigator's research effort has been to elucidate the relationship of the mesocortices with the isocortical association areas and the allocortices that form the hippocampal formation. A profitable addition to the aims, that has evolved over the past 5 years, has been to cast the patterns of pathology in Alzheimer's disease in the perspective of results from experimental neuroanatomical studies. Nonhuman primate experimental studies, which remain the core of the grant, establish the connectivity of mesocortical neurons, and pathological studies serve to establish their probable disruption in a naturally occurring human illness that targets the mesocortex. Five areas of the mesocortex will receive further investigation. These include the temporal polar, entorhinal, perirhinal, occipitotemporal and posterior cingulate cortices. The aims of experimental studies in monkeys will focus on the origin of mesocortical axons that project to cortical association areas with regard to their topography, laminar organization and the segregation of projection neurons into discrete and nondiscrete populations. Investigations relating to Alzheimer's disease will examine the cytoarchitectural homologues of these areas in the human brain, with a focus on the topography and laminar organization of pathology using both standard pathological stains and the monoclonal antibody Alz-50. Motivated by previous progress, it is hypothesized that mesocortical neurons that interconnect the cortical association areas with the hippocampal formation are targeted for pathology in Alzheimer's disease. Disruption of this relationship in neurological disease yields debilitating disorders of memory, emotion and attention. The individual investigations are cost effective and draw in part on a large collection of experimental material gathered by the principal investigator over the past 19 years ar Harvard Medical School (1969-1978) and the University of Iowa (1979-present). Additionally, complete temporal lobe blocks from over 70 cases of Alzheimer's disease processed in the principal investigator's laboratory over the past 7 years are available.