Neil W. Kowall, MD - US grants

The purpose of the Boston University Alzheimer's Disease Center (BU ADC) is to promote research on Alzheimer's Disease (AD) at BU and throughout the country by providing information and materials from well characterized patient, control and caregiver populations drawn from the ambulatory and late-stage suburban population at the Bedord VA Medical Center and the racially, ethnically, and culturally diverse poor urban Registry of the Clinical Core are assessed annually with a standardized neurological examination and neuropsychological test battery. Blood is obtained and stored for molecular genetic studies. A detailed family neuropsychological test battery. Blood is obtained and stored for molecular genetic studies. A detailed family history is obtained and a separate Caregiver Registry collects annual standardized information on family and professional caregivers. This information is entered into a database for longitudinal comparisons and correlation with the progression of AD and its impact on caregivers. Subjects, data and blood/DNA are made available to qualified researchers to stimulate new research in AD and normal aging. The Neuropathology Core establishes accurate pathological diagnoses, rigorous documentation and quantitation of neuropathological changes, harvests endothelial cells, and collects, stores and disburses post-mortem tissue. The Education and Information Transfer Core supports the development of physicians and other professional caregivers to improve clinical and research skills related to AD and provide outreach programs to increase caregivers' and the lay public's knowledge of AD. Nationally, this Core collaborates with other ADCs, ADEAR Center, Alzheimer Association and other groups to advance AD care, education, and research. The Murine Breeding and Molecular Genetics Core maintains a transgenic mouse colony as well as several colonies of mice with AD-related phenotypes including: 1) increased or decreased susceptibility to oxidative injury 2) Calreticulin Knockout mice 3) over expression or under expression of APOE. This comprehensive breeding facility is a unique resource for investigators. The BU ADC funds pilot projects to promote new AD research and fosters the development of new AD investigators. These multiple activities are coordinated by the Administrative Core. The BU ADC has greatly strengthened and expanded AD research at BU and has facilitated the involvement of African Americans in aging and dementia research. The BU ADC has promoted and supported AD research on a comprehensive range of topics including pathogenesis, animal models, neuropathology, genetic and environmental risk and protective factors, late-stage dementia, and the impact of disease burden on caregivers and society.

laboratory mouse

PROJECT SUMMARY (See instructions): The primary goal of the BU ADC Clinical Core is to provide resources and infrastructure to facilitate clinical research in Alzheimer's disease (AD) and related disorders, such that data and well-characterized research subjects are widely available and shared with other investigators and institutions. During the current funding cycle of the BU ADC, Clinical Core faculty have made major contributions in several important and innovative areas of investigation, which include three general themes: (1) Alzheimer's disease (AD) genetics and genetic risk disclosure; (2) medical and environmental risk factors for cognitive aging; and (3) the longterm effects of repetitive head trauma in the development of neurodegenerative disease. Core faculty have led or participated in several high profile national studies and have facilitated and made possible major breakthroughs in AD-related research both locally and nationally. The longitudinal Patient/Control Registry is now fully subscribed with over 450 active participants and a wide variety of clinical research studies are being actively supported. Over this past cycle, there have been 1374 referrals of registry participants to other studies with 752 enrollments to a total of 38 unique research projects. The Specific Aims of the Clinical Core for the next five years are: Specific Aim 1: To support innovative clinical AD research by identifying, recruiting, and thoroughly characterizing subjects willing to participate in clinical trials and other cutting-edge clinical research studies. We will leverage our resources to promote and accomplish wodd-class AD-related research at BU through our partnerships with the Center for the Study of Traumatic Encephalopathy and the Framingham Heart Study and through our role as a leading site in national NIH and industry supported clinical research. Specific Aim 2: To establish research-quality diagnoses on all participants through multidisciplinary diagnostic consensus conferences and to collect and submit high quality data to the Data Management and Statistics Core (DMSC) for timely UDS submissions to the NACC database and for data sharing with qualified AD investigators engaged in cutting edge AD-related research. Specific Aim 3: To collect, store, analyze, and distribute biological samples from registry participants for APOE genotyping, DNA banking, and biomarker assays, to support high priority AD-related research. Specific Aim 4: To collaborate with the neuropathology and education cores to maximize CNS tissue donation for clinicopathological correlations and for other state of the art tissue-based research.

PROJECT SUMMARY (See instructions): Core Description: The Education and Information Transfer Core (EITC) leads outreach, recruitment, and retention activities that support the Boston University Alzheimer Disease Center's (BU ADC) clinical research portfolio. In addition, the EITC provides Alzheimer's disease (AD)-related education to both professional and lay audiences. During the current funding cycle, the EITC has developed two specialized areas that complement its Core functions, including: (1) developing and implementing innovative programs to increase our African American participants' involvement in the Center's brain donation program, and (2) enhancing our Center's long-standing professional education focus with the successful replication of a medical student education program developed by our Northwestern University EITC colleagues. The BU-based program (known locally as the PAIRS Program) partners first-year students with community-based patients with early stage AD for an experiential learning opportunity. These two areas of specialization will continue into the proposed renewal period and are well integrated into our EITC specific aims for the next cycle. Specifically, we aim to: (1) Facilitate and evaluate outreach efforts in the recruitment, referral, and retention of participants in the BU ADC research registry and BU ADC-sponsored clinical research projects with an emphasis on the recruitment and retention of individuals with mild cognitive impairment (MCI) and earlystage AD and the recruitment of African American participants into the Center's brain donation program; (2) Provide lay audience education about AD and related disorders through community-based outreach in collaboration with other BU ADC Cores and community partners; and (3) Facilitate education and a high quality training environment for professionals at all career levels interested in clinical and translational research and the clinical care of individuals with MCI, AD, and related disorders. These aims will be met through numerous academic and community partnerships, professional and lay audience educational events, formal professional education programs, a biannual newsletter, and an active and highly-utilized website.

PROJECT SUMMARY (See Instructions): A strong and responsive Administrative Core is a key component of the Boston University Alzheimer's Disease Center (BU ADC). The Administrative Core consists of a formal administrative structure under the leadership of the BU ADC Director, Dr Kowall. Three standing administrative committees have been established: the Executive Committee, the External Advisory Committee, and the Community Action Council and an ad hoc Internal Advisory Committee. In conjunction with the Center Director, these committees are responsible for coordinating, planning, overseeing, and evaluating all BU ADC activities and ensuring the optimal utilization of BU ADC resources. The budget for the Administrative Core supports centralized administrative personnel and activities relevant to the overall mission of the BU ADC. The budgets for other administrative functions assigned to specific cores are included in individual core budgets. The aims of the BU ADC administrative core are: 1. To integrate, coordinate, direct and plan all BUADC activities and to ensure full compliance with all human subjects, animal welfare, scientific integrity, and financial policy requirements of NIH while promoting a culture that values and promotes the highest standards of ethics in clinical care and research guided by input from the scientific and lay communities. 2. To foster innovative AD research through a strong pilot project program, by facilitating cross-core interactions, and by maximizing resource utilization to support affiliated programs such as the Framingham Heart Study and the Center for the Study of Traumatic Encephalopathy. 3. To partner with the local, regional, national and international AD research community to support high impact research including the Framingham Heart Study, ADNI, ADCS, AD genetics consortium, and industry sponsored clinical trials. To ensure that all mandated data sets, such as the UDS, are submitted to NACC in an accurate and timely manner. 4. To support and inform the communities we serve regarding the benefits of the BU ADC and AD research. We have an active and engaged Community Action Council, have a longstanding and strong affiliation with the Massachusetts Alzheimer Association, and actively partner with Continuing Care Retirement Communities in the greater Boston area.

Since 1996, the BU ADC has been a catalyst for research on brain aging and Alzheimer's disease (AD) at the local and national levels. The BU ADC is an active contributor to all major national AD initiatives through its contribution of large numbers of samples and standardized clinical data collected from well-characterized participants. The BU ADC also contributes participants to important national interventional AD clinical trials including the A4 study. Research supported by the BU ADC has helped to better define normal brain aging and the transition from normal aging to mild cognitive impairment (MCI) and to the earliest stages of dementia. In the current funding cycle, the BU ADC has been a leader for innovative research at the intersection between brain trauma, aging, and cognitive decline that paved the way for two new major NIH U01 programs on Chronic Traumatic Encephalopathy (CTE) based at BUSM. A major focus of BU ADC supported research over the next funding cycle will be to build on this strong foundation by: (i) differentiating AD and CTE in prodromal and later stages in aging subjects, and (ii) determining the role of repetitive head injury in the evolution of AD. The BU ADC is composed of 5 interactive and synergistic cores: Administrative, Clinical, Neuropathology, Data Management & Statistics, and Outreach and Recruitment, and a Research Education Component. The BU ADC actively partners with the Alzheimer Association in advancing AD-related research and the Concussion Legacy Foundation in advancing research on the long-term effects of brain injury. The overall specific aims of the BU ADC are: 1) to identify, recruit, and thoroughly characterize MCI, AD, CTE, and control subjects willing to participate in cutting-edge research studies and clinical trials. Research quality MRI, amyloid and tau PET scans, and CSF collection will be performed on a subset of participants; 2) to collect, store, analyze, and distribute biological samples from participants for APOE genotyping, DNA banking, biomarker assays to support high priority AD and CTE research; 3) to conduct state-of the-art diagnostic neuropathological evaluation and provide high-quality tissue for research on AD, CTE and related conditions; 4) to educate the next generation of research leaders through the Research Education Component and to foster the professional development of early-stage investigators and innovative AD and CTE related research through the BU ADC pilot project program; and 5) to collect and store high quality data, ensure data security and integrity, and provide biostatistical consultation for investigators affiliated with the BU ADC. The Administrative Core coordinates activities of the BU ADC cores to achieve the above aims and serves as the interface between internal ADC activities and external entities and ensures that BU ADC activities are consistent with the NIA ADC program mission. The BU ADC is unique in its research focus on the role of brain trauma in neurodegeneration and will make available to the research community unmatched resources to support research on AD and the role of brain trauma in age-related neurodegeneration.

Please refer to Research Strategy for all changes and additions to original Aims.

The Boston University Alzheimer's Disease Research Center (BU ADRC) is committed to the goals and strategies of NAPA including: to prevent and effectively treat AD and AD related dementias (ADRD) by 2025 by expanding AD/ADRD research; to accelerate efforts to identify early and pre-symptomatic stages of AD/ADRD; and to educate the public about AD/ADRD. BU ADRC research themes are congruent with NIH AD/ADRD Research Summit recommendations including: 1) research on heterogeneity and the multifactorial nature of AD/ADRD; 2) molecular profiling of existing and new cohorts; and 3) developing new public-private partnerships. We operationalize our mission through 7 tightly integrated cores: Administrative, Clinical (CC), Data Management and Statistics (DMS), Biomarker, Neuropathology (NPC), Outreach/Recruitment, Engagement (ORE), Genetics and Molecular Profiling (GMP) and a research education component (REC). The Cores are focused on cutting edge research, proactive community engagement, training the next generation of AD/ADRD clinicians and researchers, and sharing key material, data, and expertise both among key partners and with the community at large. The BU ADRC has made significant contributions to the remarkable growth of AD/ADRD research nationally and has actively contributed participants, biological samples, clinical data, and scientific expertise to all major national AD/ADRD research initiatives. The BU ADRC has been the catalyst for exciting new research on genetic and lifespan environmental risk factors and AD/ADRD, particularly vascular risk and exposure to repetitive head impacts (RHI) from contact sports, military service and other sources. Major BU ADRC research themes include studies on RHI from contact sports and military service and risk for AD/ADRD, including chronic traumatic encephalopathy (CTE) and deep phenotyping AD/ADRD heterogeneity with a range of complementary innovative approaches including digital and EEG phenotyping; neuropathology; genetics; biostatistical modelling; biomarker discovery; and molecular profiling. The BU ADRC will build on this strong record of accomplishment to support new research and educate the next generation of AD/ADRD scientists. The BU ADRC will also support high risk high gain innovative developmental projects focused on NAPA and NIA strategic goals and utilize our collective expertise and experience to facilitate career development of investigators with diverse backgrounds. The BU ADRC will develop new partnerships and enhance current partnerships with other ADRCs and national research programs, foundations, advocacy groups and private organizations in our quest to prevent and treat AD/ADRD. Exposure to RHI is associated with CTE and a wide range of other AD/ADRD pathologies. As recognized leaders in this space, we are uniquely positioned to support research on genetic and other risks factors and study how RHI affects the clinical course, biomarker profile, and clinical-pathological features of AD/ADRD including CTE.