In 1997, the FHS began its brain donation program, and has 568 currently enrolled subjects and 241 who have come to autopsy. As a community-aging brain bank, there is a spectrum of pathologies present, including a significant number of participants that were cognitively intact at the time of death (e.g., CDR 0; 32%), mild cognitively impaired (19%), or demented (48%), including 34.2% with possible or probable AD. This spectrum of disease allows for the study of heterogeneous pathologies on clinical outcomes. Traditional pathological methods used to characterize the distribution of amyloid and tau throughout the brain are semi-quantitative and the diagnosis of AD is dependent on meeting specified thresholds of density and regional involvement. Neuropathological characterization of vascular disease into standard quantification methods is still not uniform and quantification of other pathologies (e.g., Lewy bodies, hippocampal sclerosis, argyrophilic grain disease, etc.) relies on estimation of regional density and a summary impression of overall distribution patterns. Accurate assessment of pathological burden is further complicated by the prevalence of mixed pathologies, which increases with advanced age. Digital technologies offer an exciting opportunity to attenuate the limitations of traditional semi-quantitative methods and provide a level of measurement that is significantly enhanced in its precision and objectivity. The proposed Neuropathology Core proposes to continue neuropathological characterization of FHS participants who come to autopsy integrating longitudinally applied semi-quantification methods with new technologies to allow precise quantification of AD and cerebrovascular pathologies.
The aims of the Neuropathology Core are (1) perform state-of-the-art diagnostic neuropathology, (2) develop novel methods for qualitative and quantitative histopathological characterization of the tissue, (3) optimally store and distribute brain tissue, and (4) provide neuropathological data for Project 3 and other ancillary studies by both Framingham Heart Study-Brain Aging Program (FHS-BAP) and external investigators. FHS' neuropathological protocol is already aligned with the Boston University Alzheimer Disease Center (BU ADC) in biospecimen collection, blocking, staining and storage, and will be further aligned with 7 other brain bank cohorts through a newly funded U54 led by Neuropathology Core Leader, Ann McKee and co-Leader Thor Stein. In addition, a digital library of the pathology slides will be generated for each participant and through the Data Core, will be made publicly available.