Symptoms of parkinsonism and dementia frequently occur together, raising the question as to whether Alzheimer's disease (AD) and Parkinson's disease (PD) are two ends of a spectrum or unrelated entities that occur together by chance. The more recently recognized Lewy body disease (LBD), as a presumptive third entity, may also produce a clinical and pathological syndrome that can resemble either PD or AD, further complicating definition of the relationship between the disease processes. It is unknown whether LBD is simply an overlap syndrome between AD and PD, a variant of either AD or PD, or a distinct entity with it's own pathogenesis. The purpose of this investigation will be to use quantitative morphometry to study the neuropathological features in post mortem brains of patients with parkinsonism and dementia to determine whether there are quantitative pathologic features that separate LBD from AD and from PD. The principal investigator will obtain quantitative estimates of neuronal loss amyloid deposition, neurofribrillary tangles, neuritic degeneration and Lewy bodies in nine brain regions. We will then determine whether specific clusters of these features can be identified that distinguish the disease processes(es) of PD, AD and LBD as a spectrum or as two or three discrete conditions. The availability of brain tissue from patients with autosomal dominantly inherited forms of AD will also enable the PI to scrutinize the value of the clinical semiology and pathologic findings in cases of parkinsonism and dementia where specific etiologies have been identified.
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