PROJECT SUMMARY – NEUROPATHOLOGY AND BIOCHEMISTRY CORE Neuropathologic evaluation remains an important part of clinical and translational research on dementia with Lewy bodies (DLB) and Parkinsonian disease dementia (PDD), disorders that have been grouped in the research recommendations of NIH-sponsored Alzheimer Disease and Related Dementias (ADRD) recommendations as the Lewy body dementias (LBD). The purpose of the Core B: Neuropathology is to perform quantitative postmortem neuropathologic evaluations and data collection for all LBD brains that will be distributed to the CWOW scientists. The Core B will provide pulverized frozen human brain samples, brain homogenates, purified protein preparations (Aβ and α-Syn) or paraffin sections of LBD cases and matched controls to all CWOW investigators, as well as to qualified investigators at other research institutions as approved by the Executive Committee of Core A and the Mayo Clinic Biospecimen Committee. The quantitative traits generated include counts of cortical Lewy bodies, semiquantitative estimates of substantia nigra neuronal loss, dopaminergic deficiency in putamen with tyrosine hydroxylase immunohistochemistry and counts of senile plaques and neurofibrillary tangles in cortical and subcortical areas with thioflavin S fluorescent microscopy. Core B will perform digital microscopy and image analysis on sections processed for immunohistochemistry for α-Syn, phospho-tau and Aβ40, Aβ42, as additional other quantitative endophenotypes, such as phospho-TDP-43.