Although a defined clinical phenotype is used to distinguish Alzheimer's disease (AD) from other late-life dementias, the accuracy of antemortem tests for the diagnosis of AD are imperfect. Ultimately, AD is defined most securely when the clinical phenotype is coupled with the postmortem detection of specific brain lesions considered to be """"""""pathological signatures"""""""" of AD. Uncertainty about the antemortem diagnosis of AD is likely to impede efforts to develop and test potentially useful therapies. Indeed, as many as 20% of elderly patients with a dementia ascribed to AD will fail to exhibit postmortem evidence of the neurofibrillary tangles (NFTs) and senile plaques (SPs) identified as hallmarks of AD. This subset of elderly patients with an AD-like dementia, but no AD pathology, may exhibit lesions characteristic of Pick's disease, diffuse Lewy body (LB) disease (DLBD) or other neurodegenerative diseases associated with profound cognitive dysfunction. The consistent assignment of elderly demented patients followed by the Clinical Core (Core B) of this ADCC to 1 of several diagnostic categories (e.g. AD, DLBD) is central to the mission of this ADCC. Hence, the goal of the Neuropathology Core (Core C) of this ADCC is to obtain and thoroughly characterize postmortem tissues from all deceased ADCC patients for whom permission for an autopsy is obtained. Complete autopsies will be performed and objective criteria will be used to sort the cases into well defined diagnostic categories. Further, all of the vital information on this case material (e.g. age of the patient, diagnosis, postmortem interval, means of tissue denaturation, tissue recipients, etc.) will be recorded in an electronic data base for correlation with clinical data obtained on these patients in Core B. Finally, Core C will serve as a resource to other investigators in this ADCC, a related Program Project (""""""""Molecular Substrates Of Aging & Neuron Death"""""""", P01 AG-09215) on AD and idiopathic Parkinson's disease (PD), and new research projects on AD stimulated by the presence of this ADCC at the University of Pennsylvania.
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