Core C: Resource Core

Resource Core: Abstract Nearly all neurodegenerative disorders are characterized by progressive accumulations of pathological deposits of disease protein aggregates within cells, blood vessels or in the neuropil. These deposits are the signature CNS lesions that define these disorders as exemplified by specific alpha-synuclein aggregates which are required for the postmortem diagnosis of Lewy body disease. However, Alzheimer’s disease neuropathologic change consisting of amyloid plaques and neurofibrillary tangles in addition to TDP-43 proteinopathy also contribute to cognitive dysfunction in the setting of Lewy body disease. A major focus of this Resource Core is to provide resources to investigators and collaborators in support of scientific studies to better understand the mechanisms that cause dementia in Lewy body disorders. A comprehensive post- mortem brain examination of individuals followed longitudinally in the Clinical Core provides definitive classification of the underlying neuropathology using standardized criteria in addition to the exhaustive documentation of co-morbid neurodegenerative disease pathologies in each case irrespective of clinical phenotype. Fixed and frozen tissues, DNA, biofluids and alpha-synuclein proteopathic seeds are banked and distributed to investigators in all four projects to further both clinicopathologic and basic research studies. Thus, this Resource Core is a vital component of this Program Project Grant by grounding mechanistic research projects to the human disease by use of human and recombinant resources in support of the overall goal of better understaning how genetic, biochemical and pathologic alpha-synuclein diversity drives cognitive dysfunction and dementia.