The Administrative Core provides the leadership, administrative mechanisms and oversight to enable the USC ADRC to achieve its overall aims and foster core interactions of the center. The Administrative Core is dedicated in supporting the USC ADRC missions by providing clear communication channels, strategically allocating resources, carefully managing the budget, and consistently ensuring compliance with all regulatory and participant safety standards. The Administrative Core has 4 specific aims:
1) Guide the scientific direction of the ADRC around its three overarching scientific goals to recruit and follow a clinical cohort that is enriched for carriers of APOE ε4, promote local ADRD research at USC, and further national collaborations.
2) Coordinate fiscal, operational, and regulatory functions across all cores to ensure appropriate, optimal, and effective utilization of center resources.
3) Promote participation across all Cores in collaborative national research initiatives, including NACC, NCRAD, ADGC, ADNI, ACTC, DVCID, ACAD, SCAN, and CLARiTI, leveraging our metabolic, vascular disease, and neuroimaging expertise to clarify factors that modify the effect of APOE ε4 on cognitive decline and AD biomarkers.
4) Attract early-stage and new investigators, and Support Training and Education through mentorship, development projects (DP), seminars, and research symposia and provide public education on the importance of understanding and addressing genetic, metabolic and vascular risk profiles for brain health.
The Biomarker Core unites ADRC efforts to standardize the collection and analysis of biofluid samples and brain imaging, along with the sharing of biomarker resources and derived data. In addition to serving as a hub to support these efforts for ADRC participants, we also support collaboration with academic and commercial collaborators. Our ADRC has previously focused on vascular factors related to AD and we aim to expand that focus to characterize factors that modify the effect of APOE ε4 on cognitive decline and ATN(vi) biomarkers, emphasizing vascular, lipid, inflammatory, genetic, and ethnic influences. The Biomarker Core is led by Robert Rissman PhD, and supported by resources at the USC Zilkha Neurogenetics Institute (ZNI) in Los Angeles, and the USC Alzheimer Therapeutics Research Institute (ATRI) in San Diego. The Biomarker Core has 3 specific aims:
Aim 1: Biofluid collection, processing, storage and sharing.
1) Coordinate collection, processing and storage of CSF, blood, plasma and DNA from ADRC Clinical Core participants using national ADRC Best Practices SOPs.
2) Perform analyses of CSF, plasma and DNA relevant to ADRD using validated methods to facilitate characterization of the ADRC cohort.
3) Provide ADRC samples and core resources (bioassay, DNA analyses, extractions, processing pipelines) to a broad array of investigators in support of new research projects and foster career development of scientists in biomarker research. Provide expertise for training in biomarker methods.
Aim 2: Facilitate biomarker research through an integrated informatics toolkit: Maintain a state-of-the-art biosample inventory linked with the ADRC DMSC to provide internal and external investigators with CSF and plasma samples, DNA, and derived data in support of ADRD research and novel biomarker discovery.
Aim 3: Accelerate local, national and international biomarker discovery efforts: Leverage ADRC biospecimens to develop new methods that inform on neuropathology, diagnosis, progression, prognosis and other research applicable to ADRD.
1) Leverage ADRC specimens for discovery projects at USC and nationally.
2) Work with Industry partners to develop and validate novel assays and platforms. We will also continue to support extensive collaborations with national and international investigators and train fellows, residents, graduate and undergraduate students in biomarker discovery.
The clinical core develops and maintains the clinical enterprise serving the ADRC’s overarching themes, including factors that modify the effect of APOE ε4 on dementia and ATN biomarkers, emphasizing vascular and metabolic risk. The core supports the ADRC’s overall scientific goal, i.e., understanding mechanisms by which APOE genotype affects clinical phenotype and progression toward dementia. The core provides well-characterized, longitudinally followed participants for affiliated research projects, USC researchers, and the broad scientific community by developing and maintaining a cohort at risk for dementia or its underlying pathology, characterizing participants by fluid and imaging biomarkers, and encouraging consent for brain donation. The core maintains an active registry of “study ready” potential participants who expressed interest in research participation. The core contributes to national initiatives including NACC, NCRAD, ADGC, SCAN, and CLARiTI; to multi-site observational studies including ADNI, DIAN, MarkVCID, DVCID, ACAD; and to national and international trials including the USC ACTC, UCSD ADCS, A4 and AHEAD 3-45. The core catalyzes local research by supporting recruitment, providing oversight and training for investigator-initiated studies and trials (e.g., PPGII, DVR, NoMAD, GADSIL, DHA, phenserine, exosomes). To accomplish its mission, the core closely interacts with other ADRC cores: Major science findings supported by the core are discussed in the proposal. Thus, the clinical core supports the USC ADRC’s overarching goals
A) defining factors that influence the effect of APOE ε4 on cognitive decline and ATN biomarkers,
B) supporting local ADRD research, and
C) contributing to national research initiatives.
The overall objective of the Data Management and Statistical Core (DMSC) is to provide high quality services and resources to the Administrative, Clinical, Neuropathology, Biomarker, Imaging, and ORE Cores, the Research Education Component (REC), and ADRC faculty (including investigators involved in ADRC projects, development projects, and ADRC-affiliated investigators). The DMSC resources provides an informatics and statistics environment to support cutting-edge dementia research both locally and nationally. There are four aims to this Core:
1) Data management. Focused on the provision of F.A.I.R. data management framework for ADRC-related research This effort will be built upon a unified ADRC archive that houses and integrates all ADRD research projects and programs at USC.
2) Program coordination with national efforts ensuring timely and accurate data entry to NCRAD, ADGC, SCAN, CLARiTI and GAAIN (Global Alzheimer’s Association Interactive Network), among others.
3) Biostatistical support in the design, coordination and analysis of ADRC-related projects, including development projects supporting the REC, design of clinical studies and trials, integration and analysis of multimodal data, and support for data interpretation and manuscript preparation.
4) Education & training (in concert with the ORE Core and REC) via practical and didactic experiences on relevant study designs, statistical models, and informatics concepts and practices to trainees and investigators involved in dementia-related research. Finally, we will provide communications and documentation via the ADRC website.
As a part of the USC Alzheimer Disease Research Center competitive renewal, the Imaging Core continues to serve the overall mission to provide high-quality MR and PET imaging resources. The main goal of the Imaging Core is to provide a standardized imaging protocol across ADRC following the Standardized Centralized Alzheimer’s & Related Dementias Neuroimaging guidelines (SCAN). The ADRC Imaging Core also provides core resources, including MR physics and PET expertise, multi-scanner sequence and protocol development, image data quality control and management, research collaboration, and a global framework for conducting AD neuroimaging research. The Imaging Core is led by a well-integrated and collaborative team, including Arthur Toga (Core Leader), Kirsten Lynch (Core Co-Leader), Yonggang Shi, and Meredith Braskie who together provide expertise in vascular, functional, and structural imaging and its analyses for 3T and 7T MRI, and PET. We have 5 specific aims where the Imaging Core provides a standardized imaging framework for all ADRC; perform high quality control of all imaging data; develop technical and scientific approaches for ultra-high field 7T MRI; assist in PET protocol development and quality control; and conduct education and training in modern imaging techniques. Taken together, these goals will serve the USC ADRC’s overarching goals to:
1) Recruit and follow a clinical cohort that reflects the population of Los Angeles and is enriched for APOE ε4, focusing on factors that modify the effect of APOE ε4 on cognitive decline and AD biomarkers,
2) promote local ADRD research at USC, and
3) further national collaborations.
The Neuropathology (NP) Core provides gold-standard neuropathologic diagnoses for the USC ADRC participants and banks fresh and frozen nervous system tissue for distribution to support ADRD researchers inside and outside of USC. The NP Core houses tissue from >1,100 cases. Tissue provided by the Core is unique among ADRC repositories in the exceptional variety of tissue (e.g., eyes, spinal cord) available. Each case is reviewed independently by the two Core leaders (Drs. Annie Hiniker and Debra Hawes, both board-certified neuropathologists) who apply NACC 11 standards for diagnosis and then re-review together to reach consensus if needed. Each case will be stained for H&E, phospho-tau (AT8), beta-Amyloid (4G8), α-synuclein, and TDP43. Diagnostic stains available and utilized as needed are AT8, RD3, and RD4 for tau species, 4G8 for Abeta, anti-alpha-synuclein for Lewy bodies, Iba-1 for macrophages, GFAP for gliosis, and neuronal markers including NeuN and NSE. Drs. Hiniker and Hawes are expert in developing and implementing new immunostains and new markers will be added as appropriate for refined diagnoses and research applications. Under the leadership of Dr. Hiniker and Dr. Michael Bienkowski, an expert in digital pathology, the Core will collaborate with the DMSC Core to develop an accessible digital pathology library of our autopsy cohort of >1,100 cases that will be ultimately integrated with genetic and biomarker data from the Biomarker Core. The NP Core contributes to our Center’s studies of the effects of APOE genotype on ADRD, particularly focusing on the relationship of APOE genotype to vascular pathology and perivascular inflammation. The Core also measure the detailed contributions of APOE genotype to pathology and cognitive impairment in collaboration with the Clinical Core. Finally, NP Core faculty support mentoring and training in ADRD and collaborate with the REC to educate students, residents and fellows in the pathologic diagnosis of ADRD.
The overall objective of the Outreach, Recruitment and Engagement Core (ORE Core) is to serve as the primary bilingual and bicultural resource and liaison between the USC ADRC, our study participants, their caregivers/partners, and the larger community, i.e., the general public, people living with dementia and caregivers, professional care providers, and the lay community in Los Angeles County. The ORE Core facilitates bidirectional communication through our signature outreach and engagement activities, USC GeneScreen registry, and recruitment from the LA County Department of Health Services (DHS). We will:
Aim 1: Engage in Participant Recruitment & Develop a Research Registry: The ORE Core will maintain and further develop USC GeneScreen, a registry of persons in the LA County area interested in participating in studies and enriched for APOE ε4 carriers. We will augment Latino participation (English, Spanish, low socioeconomic status) in the registry given the higher prevalence and disease burden in this population and our catchment area composition. During the next 5 -years, our goal is to genotype and register a diverse pool of 1500 participants who are “study-ready” to enroll in AD/ADRD research.
Aim 2: Enhance Recruitment from the LA County Department of Health Services (DHS) at the Rancho Los Amigos National Rehabilitation Center (RLANRC). Our ADRC is affiliated with the California Alzheimer’s Disease Center (CADC) based at RLANRC, an integral part of the DHS safety-net community health system whose goals are to ensure quality health care for all regardless of socioeconomic status. Through work there, we will identify and invite RLANRC patients with MCI or mild dementia to participate in ADRC research studies.
Aim 3: Continue to Engage in Bidirectional Education, Information and Resource Sharing: In collaboration with our extensive network of community partners, we will continue to serve as a community resource in targeted engagement and educational outreach to the public-at-large, healthcare and human service providers, potential study participants, and current participants. We will communicate the latest ADRC- and AD/ADRD research findings and timely information on brain health, aging and wellness.
The mission of the University of Southern California (USC) Alzheimer’s Disease Research Center (ADRC) Research Education Component (REC) is to direct the scientific careers of scientists from multiple disciplines into a career in Alzheimer’s disease and related dementias (ADRD) research. Co-directed by Hussein Yassine and Duke Han and leveraging unique training programs and research resources in the USC academic environment, REC scholars will be trained with an emphasis on age-associated vascular/metabolic processes that affect brain health and ADRD risk in APOE ε4 carriers and the population in Los Angeles (LA) County. Through the USC ADRC REC, trainees are exposed to an annual program where they are introduced to mentors, oriented to existing ADRC resources (imaging data, clinical trial and longitudinal data, and tissue samples), and provided with an opportunity for development project funding support. We integrate current post-doctoral and junior faculty trainees at USC from relevant training and academic programs. ADRC scientists are mentored in how to advance their career in ADRD research within the context of multidisciplinary collaborations with experts in biostatistics, neuropsychology, medicine, gerontology, sociology, demography, economics, computer science, and social work. This program supports scientifically informed research on older adult populations and prepare scientists to become independent researchers through three Specific Aims:
1) Support ADRC scientists through a multidisciplinary training program integrated with the USC RCMAR led by Julie Zissomopoulos, development project funding, and an annual symposium.
2) Support the career development of one post-doctoral investigator who has shown professional promise for a 2-year post-doctoral fellowship sponsored by the USC Keck School of Medicine Dean’s office. The fellowship will be focused on AD risk in large and small populations.
3) Monitor the progress of ADRC scientists during the period of the award as well as through their early career milestones (e.g., receipt of an independent grant). ADRC scientist alumni will be supported through continued involvement in activities that support and improve both their career opportunities and the experience of the next cohort of development project grantees. To date, the USC ADRC REC has successfully contributed to the development of multiple early career and junior scholars devoted to ADRD research. The continued success of this program will be monitored by the degree to which the scientific career trajectories of the investigators are successful, specifically with respect to an ADRD research focus and extramural funding.