ADRC/ADRD Developmental Project Program
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ADRC Developmental Project Program
The Duke/UNC ADRC promotes research and discovery in Alzheimer’s disease and related dementias through its core resources.
The purpose of the ADRC developmental project program is to stimulate and support, innovative, high potential lines of research related to our them: to identify age-related changes across the lifespan that mediate the development, progression, and experience of Alzheimer’s disease.
Developmental Project Program Awardees
July 1, 2022 – June 30, 2024
Associate Professor of Neurology at UNC Chapel Hill
Associate Professor of Neurology at Duke University
Project Title
Linking LRRK2 To Tau Pathology: A New Therapeutic Pathway In AD
Research Description
This is the first study to implicate LRRK2 as a driver of tau mediated dementia. Our Duke/UNC collaborative team will explore whether modifying LRRK2 kinase impacts tau pathology in mice and human neurons. This concept could identify LRRK2 therapeutics as unanticipated agents for AD patients. Therefore, our study could unify a common mechanism that is relevant to, not just one, but many neurodegenerative diseases encompassing AD and PD, as well as a spectrum of related disorders.
Simon Gregory, Ph.D.
Professor of Neurology, Duke University
Project Title
Profiling the molecular pathology of Alzheimer’s disease
Research description
Our overarching hypothesis is that cells in different brain regions have variable molecular identities that respond differently to amyloid plaque accumulation and that characterization of these differences can lead to an understanding of AD progression. To test this hypothesis, we will explore gene expression response to amyloid plaque and NFT accumulation by performing spatial transcriptomics and in situ sequencing in different brain regions from controls and age/sex matched individuals with histopathologically determined AD.
Shih-Hsiu “Jerry” Wang, MD
Assistant Professor of Pathology, Duke University Medical Center
Project Title
Interrogating the pathogenic mechanisms linking age-related TDP-43 pathology, cerebrovascular pathology, and Alzheimer’s disease in the aging brain
Research Description
Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a common brain pathology of aging, characterized by accumulation of TDP-43 inclusions in the limbic system. LATE is present is approximately 30-40% of aging brains and is a significant cause of dementia, independent of Alzheimer’s disease (AD) or other brain pathologies. The cause of LATE is currently unknown, but there is a strong association between LATE and a specific form of cerebrovascular pathology, called arteriolosclerosis. This project uses brain tissue from the Bryan Brain Bank to examine the link between arteriolosclerosis and TDP-43 pathology and identify molecular changes that distinguish LATE from AD and other related dementias
July 1, 2023 – June 30, 2024
Associate Professor of Neurology, UNC Chapel Hill
Associate Professor of Surgery, Duke University
Project Title
Impact of Gentrification and Other Measures of Neighborhood Change on Alzheimer’s Disease and Related Dementias
Research Description
The prevalence of Alzheimer’s Disease and related dementias (ADRD) is projected to triple by 2060 due, in part, to the aging population. There is a critical need to identify risk factors that can be targeted to reduce the burden of ADRD. Social support and physical activity are associated with healthy aging, and both of these are in part impacted by the contextual factors within which a person lives. These contextual factors can include neighborhood level factors, built environment, and environmental pollutants. Often termed social determinants of health, factors such as poverty, unemployment, low educational attainment, poor built environment can impact health and play an important role in health inequities. There is a growing body of research that suggests these social factors are associated with ADRD risk. There is less research on how dynamic changes to the neighborhood – such as gentrification – may impact ADRD risk. Quantifying the changing neighborhood and social milieu of negative exposures may be important to understand racial and ethnic disparities in ADRD.
July 1, 2024 – June 30, 2026
Michael DeVinney, MD, Ph.D.
Assistant Professor of Anesthesiology, Duke University
Project Title
The role of cerebrospinal fluid complement activation in delirium and post-intensive care unit long-term cognitive impairment and Alzheimer’s Disease and related dementias (ADRD)
Research Description
My work uses translational neuroscience approaches, such as cerebrospinal fluid molecular assays, sleep EEG, cognitive testing, and delirium assessment to identify mechanisms of delirium. Delirium is a syndrome of disrupted attention and consciousness that occurs in ~20% of the >19 million older surgery patients and ~50% of the >5 million intensive care unit (ICU) patients in the United States every year. Delirium is also associated with increased risk for Alzheimer’s disease and related dementias (ADRD), yet there are no FDA-approved drugs to prevent it, due to a major gap in our understanding of its underlying mechanisms. Our current work aims to discover potential mechanisms of delirium that could be targeted in future studies.
Shahzad Khan, Ph.D.
Assistant Professor of Cell Biology and Physiology, UNC Chapel Hill
Project Title
Investigation of Primary Cilia Loss in Alzheimer’s Disease
Research Description
Maintaining health and reducing disease-risk requires the brain to properly transduce signals across specialized regions and cell types. My lab utilizes mouse models, neural cultures, human brain samples, single-cell transcriptomics, proteomics, and microscopy to probe the molecular mechanisms that underlie aging and neurodegeneration. Ultimately, we aim to identify therapeutic targets for diseases like Alzheimer’s and Parkinson’s.
Cara McDermott, Ph.D.
Assistant Professor of Medicine and Population Health Sciences, Duke University
Project Title
Improving Medication Safety and Outcomes for Rural Patients Living with Dementia and their Care Partners
Research Description
Research focuses on identifying gaps in healthcare delivery and using implementation science to adapt and assess evidence-based interventions. Dr. McDermott works to optimize medication use, improve symptom management, and reduce unwanted healthcare use among older adults with multiple chronic conditions, with a particular interest in improving outcomes for patients with cancer, COPD, or dementia and their caregivers. She is particularly interested in improving shared decision making in this population and medication deprescribing for adults with serious illness. In recent projects, she investigated ways to improve end-of-life care from the perspective of bereaved caregivers and care delivery gaps leading to unwanted healthcare utilization at end of life for patients with multimorbidity
July 1, 2026 – June 30, 2028
Ahmad Hariri, PhD
Professor of Psychology and Neuroscience, Duke University
project title
A Next Generation Brain Biomarker of Accelerated Aging in Alzheimer’s Disease
research description
Integrating psychology, neuroimaging, pharmacology and molecular genetics in the search for biological pathways mediating individual differences in behavior and related risk for psychopathology
Associate Professor, Psychiatry, UNC Chapel Hill
project title
Sex-Dependent Mechanisms Linking Midlife Metabolic Function and ADRD Risk
research description
Particularly interested in the use of non-pharmacological approaches (e.g. exercise and dietary modification) to mitigate late-life cognitive impairment, with a focus on vascular and cardiometabolic mechanisms. His work has also focused on the development and deployment of behavioral treatments within chronic disease populations
Melissa Walsh, PhD
Research Instructor, Psychiatry, UNC Chapel Hill
project title
Synaptic Density Imaging in the Memory and Aging Study Perimenopausal Cohort: A Pilot PET Study
research description
My research vision is to characterize how menopausal hormonal changes shape cognitive and brain vulnerability/resilience in women with and without risk factors for Alzheimer’s disease, with a particular emphasis on hormonal mechanisms that contribute to synaptic loss.
