The Alzheimer's Disease Research Center (ADRC) at the University of Pittsburgh was established in 1985 as a mechanism for integrating, coordinating and supporting new and ongoing research in Alzheimer's disease (AD) and aging. The present proposal is a request for a 5 year renewal of the ADRC. The goal of the ADRC for the next 5 years is to provide core support for investigators and has three principle objectives. The first objective is to support and foster research into the cellular and molecular neurobiology of AD with specific reference to understanding the cellular, metabolic and molecular changes that could mediate the pathological, physiological and clinical abnormalities. This goal will be approached with studies which will investigate: A) membrane metabolic and molecular dynamics in AD and control erythrocytes (Project #2, Pettegrew) as compared to clinical symptomatology and in vivo 31P NMR findings in brain (NIA- funded, Pettegrew); B) the structural and functional comparison of beta- amyloid and epidermal growth factor peptides (Pilot Project #1, Klunk); C) excitatory amino acid transmitters and receptors in pyramidal cells and the relationship of this system to the pathology and symptomatology of AD (Project #4); D) tyrosine hydroxylase-immunoreactive neocortical neurons and their role in AD, Parkinson's and diffuse Lewy body disease (Project #5, Lewis); and E) possible pharmacokinetic mechanisms to explain the high incidence of adverse drug reactions in AD (Pilot Project #4, Perel). The second objective is to support and foster research directed at understanding the clinical syndrome of AD with specific reference to functional dissociations. This goal will be approached with studies which will investigate: A) measures of cognitive slowing in patients who present with mixed symptoms of depression and dementia (Project #1, Nebes); B) SPECT imaging of frontal and temporal cortex as a predictor of short versus long-term memory loss (Pilot Project #5, Becker); C) the effect of sleep apnea on cognitive, affective and behavioral functioning in AD (Pilot Project #3, Hoch); D) computer simulation of characteristics of dementia as compared to depression (Pilot Project #8, Webster); and E) the merits of a didactic, interactive, educational approach to educate and induce changes in caregiver knowledge, attitudes and behavior. The third goal is to support and foster mechanisms for the delivery of information generated by the Center to all ADRC investigators and to clinicians and investigators outside the University setting.
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