Neuropathology Core

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Neuropathology 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 the amyloid plaques and neurofibrillary tangles required for the postmortem diagnosis of Alzheimer's disease (AD) and related disorders (ADRD). However, Lewy bodies (LBs) and/or TDP-43 inclusions occur in ~70% of AD patients, as are other neuropathologies including aging related tau astrogliopathy (ARTAG), hippocampal sclerosis, and cerebrovascular disease. Other non-AD dementing illnesses are associated with a diverse spectrum of neuropathologic diagnoses including various α-synucleinopathies and frontotemporal lobar degeneration. A major focus of this NP Core is to define the full spectrum of co-morbid protein aggregate pathologies in the aging brain. 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 are banked and distributed to investigators to further both clinicopathologic and basic research studies on AD/ADRD. Neuropathology data is obtained in all cases which is transmitted to the National Alzheimer’s Coordinating Center in collaboration with the DMS Core. The NP Core also coordinates with the Neuroimaging Core to facilitate high resolution post-mortem MRI and to establish a digital histopathology library. The NP Core also provides advice and support to investigators including trainees supported by the Research Education Component to foster safe and informative human biosamples research. Thus, this NP Core is a vital component of the Penn ADRC in defining the complexity and breadth of neuropathologic change in ADRC subjects in support of its mission to increase research and education on AD/ADRD across the continuum from normal aging to dementia with the goal of identifying the causes of and cures for AD/ADRD.