Neuropathology Core

REVISED ABSTRACT: The Neuropathology (NP) Core serves both the Massachusetts ADRC (MADRC) and the broader research community by providing diagnostic validation of clinical assessments and providing deeply characterized tissue to investigators. The availability of tissue from the Core has been widely used by investigators working on AD/ADRD. It is well accepted now that a combination of pathologic processes underly cognitive impairment in most individuals and this is likely to also influence aspects of symptom progression and responses to emerging therapies. With our robust experience and resources, we are well positioned to use insights from autopsy tissue to understand drivers of clinical progression. The Core remains an outstanding environment in which to train clinical and experimental neuroscientists, neurologists and neuropathologists to work on ADRD and drive future advances. To complete these missions, we have four Aims. The first Aim is to contribute to neuropathologic diagnosis and tissue resources by the collection, diagnosis, collection of data, full reporting of findings – to families and relevant physicians with a CLIA- compliant autopsy report through the Clinical Core, and to the Data Core for research purposes -- and the wide distribution of samples in support of the research community. The second Aim is to develop new methods and reagents for prediction of molecular phenotyping and prediction of pace of change using cell-based methods, including patient-specific iPSCs, and cell-free aggregation methods with intention of translation to individuals along the course of their illnesses. This aim also includes extension of on-going work using RNA and proteomic analyses as part of a search for additional potential biomarkers. Finally, the Core will contribute to the development and extension to human autopsy tissue of novel tissue preparation methods including expansion microscopy and tissue elasticization. The third Aim is to train the next generation of neuropathologists and investigators, building off the Core’s long history of guiding individuals towards work in ADRD. These efforts are done with the MADRC REC. The important fourth Aim is to maximize staff and points of view with continued efforts to ensure broad representation among Core staff, through educational outreach in collaboration with ORE and Clinical Cores, and through Spanish language support for autopsy consenting and reporting.