New Approaches to Dementia Heterogeneity

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ABSTRACT The UCSF Alzheimer’s Disease Research Center (ADRC) is a major catalyst for a broad spectrum of dementia-related research conducted at UCSF and has served as a cornerstone for national and international multi-site diagnostic and treatment studies. In three previous cycles of funding under the P50 mechanism, we have organized a critical mass of dementia research and share our resources widely. We excel in clinical phenotyping, imaging, biospecimen collection, and pathologic evaluation of large and unique cohorts of early- onset AD (EOAD), frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), Creutzfeldt-Jakob disease (CJD), and healthy controls. The ADRC supports and effectively leverages additional NIH and foundation funding, philanthropy, and industry collaborations to accomplish its aims. At the UCSF Memory and Aging Center alone, ADRC clinical cohorts, data, and biosamples are currently utilized by 26 R grants, 6 K awards, 4 U grants, and 38 non-NIH grants. Projects and pilot awards have helped launch young investigator careers and major research programs. ADRC data and biosamples are utilized extensively by other ADRCs and an extensive network of collaborators. In this new P30 application, we accelerate efforts to define subtypes of healthy aging, MCI, AD, FTD, PSP, CBS, and CJD that predict specific molecular and physiological causes for dementia, improve early recognition and tracking of transitions from normal aging to dementia, and stimulate drug development and clinical trials. The ADRC will consist of seven cores: Administrative, Clinical, Data Management and Statistics, Pathology, Outreach Recruitment and Engagement, Imaging, and Biomarker and a Research Education Component. These cores will work collectively to pursue the following overarching specific aims: Aim 1: Explore the heterogeneous features of healthy aging, MCI, AD, FTD-spectrum disorders, and CJD to better understand their clinical, genetic, and molecular underpinnings. Aim 2: Leverage the valuable cohorts in the ADRC and the talented neuroscience communities at UCSF and beyond to “enhance the performance of innovative research” around diagnosis and treatment of dementia. Aim 3: Increase understanding of the unique cultural and biological features of aging Chinese and Latino Americans, while educating these communities with outreach lectures and web-based presentations. Aim 4: Develop innovative approaches to data management and biostatistics to support easy access and analysis of ADRC-related data while offering statistical support to our investigators. Aim 5: Train new leaders in dementia research with innovative education approaches and educate medical and lay communities about the heterogeneity of dementia with conferences, web-based presentations, and films. Aim 6: Create a new Biomarker Core to enhance the genomic, proteomic, and transcriptomic data captured from our extensive biospecimen collection. Aim 7: Transition to a more gender and ethnically diverse ADRC leadership by 2024.