University of Washington Alzheimer's Disease Research Center

Overall – Project Summary The UW ADRC’s scientific focus is investigating the biological underpinnings of AD and related dementias. We leverage powerful new technologies, including spatially resolved, cellular multi-omics; and iPSCs/organoids, that have huge potential to elucidate the variability of AD. They depend on deep phenotyping of biospecimen sources to maximize their value, and ultimately on well-characterized, diverse human subjects. Development of these resources requires effort sustained over years by an interdisciplinary team with strong institutional support. The UW ADRC is uniquely poised to undertake this work, combining our historical strengths with new partners, and leveraging the extensive resources of UW, and the collective expertise of the Leads and Director.The proposed framework organizing our core research resources is multi-disciplinary ADRD phenotyping. Four key disciplines to integrate are genetics, functional anatomy, anatomic/cognitive profiles, and neuropathology. The functional anatomy of the brain is a key point of integration. Our innovative neuropathology methods, including an RNA- preserving rapid autopsy protocol, a cortical sampling protocol based on functional anatomy, and systematic post-mortem MRI for tissue-imaging correspondence generate extensive tissue resources for our studies and for many studies nationally and internationally.In this period we also plan a focus on the clinical research resources needed to extend these methods to investigate the biological countering degeneration and dementia. We will develop an observational cohort that will enable deep phenotyping of participants with an informative range of cognitive reserve/cognitive resilience to Alzheimer’s disease. We will accomplish this by building on our successful engagement and recruitment of participants with a range of the factors that are known to be correlated with resilience (education, social (dis)advantage, social determinants of health, race, and ethnicity), coupled with a novel adaptive and culturally flexible memory screening platform and blood plasma biomarkers. Our Center’s philosophy is to view ADRD not only through the lens of what is lost, but also through what is spared. The relatively spared functional anatomical structures are the basis for spared capacities in ADRD (i.e. “strength-based reframing of ADRD”). This perspective permeates our Center, from motivating our interest in the biological basis of resilience, to our outreach and affiliated clinical efforts.The discoveries of this research must be relevant to all persons with memory loss, and we plan broad recruitment across race, ethnicity, and SES status to make our observational studies broadly representative. A closely related theme is bringing American Indians and Alaska Natives, specifically, into mainstream ADRD research, building on our successful efforts over the last 10 years. We plan to include diverse perspectives in our research training program, leadership succession, our staff, and our external advisers.