Biological heterogeneity in ADRD

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Abstract: Alzheimer's disease and related dementias (ADRD) represent a healthcare crisis of epic proportions as the US populations continues to age. The AD Research Centers (ADRC) and the NeuroBiobank (NBB), both funded by NIH, represent two separate networks both focused on promoting and supporting human brain research, the former focused on ADRD in well-characterized prospective cohorts with the deepest expertise and infrastructure for ADRD neuropathology, and the latter with the broadest network with well-established coordination across center, outreach pipelines, and data and tissue sharing mechanisms. The 2017 ADC Panel Recommendations included multiple focused on ADRD neuropathology, including developing mechanisms for inclusion of donors from underrepresented groups and non-demented (control) donors, increasing engagement with and opportunity for local communities to participate in brain donation, and enhancing collaborations across the ADRC and NBB networks to promote brain donation and research brain tissue utilization by scientists focused on ADRD. In response, an ADRC-NBB working group was established to explore opportunities to meet this need, resulting in formation of a pilot program to test some of these solutions. This proposal is for support of the UW site for this pilot study, which has five aims that, when successfully completed, will develop, implement, and test mechanisms across ADRC and NBB to identify and consent ADRD brain donors, including controls, in a coordinated manner nationally, to collect brains from consented donors who pass using procedures optimized for maximum tissue quality for research, to perform state-of-the-art neuropathological examination, to supplement this data with critical donor metadata through structured family interviews and medical records reviews, to share this deidentified information across the networks and with researchers across the US, and to fill data and tissue requests from these donors, based on this infrastructure, to support ADRD research. When successfully completed, this pilot study will have helped identify effective mechanisms/protocols/pipelines to support human brain donation and research that will ultimately help propel ADRD research toward mechanistic knowledge, improved diagnostic strategies, and effective therapeutic interventions.