Core D: University of Kentucky Alzheimer's Disease Core Center

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Project Summary/Abstract: Neuropathology Core The overall objective of the Neuropathology Core of the UK-ADRC is to support research on normal brain aging, presymptomatic AD, MCI, early and late AD, mixed dementia syndromes, and other dementing disorders. Autopsies will be performed by our Rapid Autopsy Team on longitudinally followed subjects from our Clinical Core. We will perform short post-mortem interval autopsies, and we will maintain a high autopsy rate. This Core is optimally tailored to help address important research questions. The Core will provide brain tissue, CSF and other biospecimens for investigators at UK, other ADRCs, and outside investigators. The Core will also provide consensus conference determined diagnoses, quantitation of neurofibrillary tangles, neuritic plaques, and diffuse plaques from 8 brain regions, Ab quantitation, Braak staging, CERAD, and NIA-Reagan Institute staging on all autopsied cases, along with evaluation of alpha-synuclein and TDP-43 proteinopathy. This brain bank has been operating continuously for over three decades with a strong track record, so special care will be taken to ensure diagnostic excellence, consistency, and continuity. The Core will maintain a tissue bank of the above specimens and frozen serum, plasma, buffy coats and CSF from living patients. Special emphasis will be placed on generating rigorous quantititative pathologic metrics from digital pathology, and providing investigators with specimens from cognitively intact control subjects with no Ab deposition and sparse tau pathology (successful cerebral aging) and many cases with mixed pathologies. Providing these samples will contribute to clinical-pathological correlation studies and cutting-edge research that include sponsored studies related to AD genomics, oxidative stress, hippocampal sclerosis/LATE, dementia with Lewy bodies, Down syndrome, and neuroinflammation. Frequent consensus conferences will be held with the Clinical, Biomarker, and Data Management and Statistics Cores to help define clinical-pathological diagnoses on all autopsied subjects. The Neuropathology Core is strongly integrated with other Cores of the UK-ADRC, and exploits unique opportunities to conduct clinical-pathological correlative studies on longitudinally followed subjects. Through these methods we will better understand normal brain aging and the transition to multi- etiology dementia with the goal of contributing to therapeutic or preventive measures. The Neuropathology Core complements the other Cores of the UK-ADRC to provide extremely essential diagnoses and tissue samples that are required for many cutting-edge researchers at the University of Kentucky and elsewhere. We will build on our track record of excellence using innovative tools related to brain autopsies, neuropathological diagnoses, tissue banking, and clinical-pathological correlation. Our specific aims are: Aim 1: Provide state-of-the-art neuropathological and biospecimen repository services Aim 2: Leverage neuropathology resources and expertise to contribute to research efforts Aim 3: Integrate with other cores to contribute to administrative, research and educational missions