Alzheimer’s Disease Research Center Developmental Projects Program | NYU Langone Health

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Alzheimer’s Disease Research Center Research Alzheimer’s Disease Research Center Developmental Projects Program

Alzheimer’s Disease Research Center Developmental Projects Program

The Alzheimer’s Disease Research Center’s Developmental Projects Program supports early-career investigators at NYU Langone who are working to advance innovative research in the area of Alzheimer’s disease and related dementias. The program is an integral part of our center’s commitment to foster the professional growth and development of the next generation of Alzheimer’s disease researchers.

This annual grant supports 2 researchers with awards ranging from $50,000 to $100,000 per year for 1 to 3 years, and encompasses a wide range of areas related to Alzheimer’s disease. These include basic, clinical, behavioral, translational, epidemiologic, educational, or caregiving-related research efforts that stand to expand our understanding of the mechanisms and development of Alzheimer’s disease. The program is especially intended to fund researchers working to establish new lines of investigation or seek validation for novel hypotheses through pilot studies or initial data collection or analysis.

Program Eligibility

NYU Langone faculty and advanced doctoral trainees are eligible to apply for the Developmental Projects Program. While the program is primarily aimed at early-career investigators, senior investigators working in areas other than Alzheimer’s disease and related dementias who wish to propose a novel project in a dementia-related field are also encouraged to apply.

For more information about the Developmental Projects Program, please contact Karyn D. Marsh, PhD, associate core leader, at karyn.marsh@nyulangone.org.

2021 Developmental Projects Program Grantee

Learn more about the 2021 Development Projects Program grantee.

Project Title: Alzheimer’s Disease Clusterin Mutations Alter Astrocyte Function

Principal Investigator: Shane A. Liddelow, PhD, Assistant Professor, Departments of Neuroscience and Physiology and Ophthalmology
Award Period: July 1, 2020–June 30, 2023

Project Rationale: Clusterin (CLU) is a cholesterol-trafficking apolipoprotein expressed mostly by astrocytes and important in lipid metabolism that supports the brain cells. Expression of CLU increases with age and progression of Alzheimer’s disease. Mutations in CLU are associated with neurodegeneration and may disrupt the ability of astrocytes to support neurons. However, how these age-related changes in CLU levels and disease-related mutations in CLU affect the ability of astrocytes to support neurons is unclear.

Project Aims: The project aims to model human CLU genetic variants in mouse astrocytes. Both risk and protective variants of human CLU will be introduced into mouse embryonic stem cells, which will then be differentiated into astrocytes. The gene expression and function of these astrocytes will be examined for evidence of changes related to Alzheimer’s disease. An additional goal is to determine whether astrocyte function is affected by age-related CLU expression levels or CLU mutations. The function of astrocytes and their interactions with other brain cells will be evaluated at two developmental time points with different CLU expression levels.

Alzheimer’s Disease Research Center Resources Used: Our center will provide funding for the proposed experimental work on this project.

Expected Results: This study will elucidate the effect of CLU on astrocyte functions in Alzheimer’s disease. It will also provide a convenient system for evaluating mutations in other genes in search for novel therapeutic targets. In the future, this system will be used to probe the functional interactions between CLU genetic variants and apolipoprotein E (APOE) and their impact on the astrocytes’ ability to support neurons and microglia.

2020 Developmental Projects Program Grantees

Learn more about the 2020 Development Projects Program grantees.

Project Title: Racial Differences in the Association of Slow Wave Sleep and Tau

Principal Investigator: Omonigho M. Bubu, MD, PhD, MPH, Assistant Professor, Departments of Psychiatry and Population Health
Award Period: November 1, 2020–April 30, 2022

Project Rationale: There is growing evidence demonstrating racial differences in biomarkers of Alzheimer’s disease. Black people have decreased cortical thickness, lower levels of circulating tau, and higher uptake on amyloid PET even after adjusting for demographics, cognitive status, and various risk factors. Recent evidence suggests that sleep may be a risk factor of Alzheimer’s disease and a biomarker of mild cognitive impairment (MCI) and dementia. Black people are more likely to experience sleep disorders and have significantly shorter slow wave sleep (SWS) and slow wave activity (SWA), which are known to be related to higher amyloid beta in cognitively normal older adults. The relationship between racial differences of sleep features and tau has not yet been studied, especially in the presence of amyloid beta.

Project Aims: This project aims to examine whether SWS/SWA is associated with regional tau PET deposition in clinically normal older adults using PET for a given level of global amyloid beta; to examine whether racial differences exist in regional tau PET deposition, especially in areas that are first to develop tau pathology; and to examine whether race-specific differences exist in association between SWS/SWA and regional tau PET deposition, controlling for amyloid burden.

Alzheimer’s Disease Research Center Resources Used: This cross-sectional study will include 100 cognitively normal subjects (50 Black and 50 White) recruited among the Alzheimer’s Disease Research Center cohort and 2 ongoing Alzheimer’s Disease Research Center–affiliated, National Institutes of Health (NIH)–supported R01 studies, with full clinical data, neuroimaging, and polysomnography. Our Administrative and Data Management and Statistics Cores will assist with recruiting; the Clinical Core is conducting clinical interviews for a majority of participants; and the Biomarker and Neuroimaging Cores will assist with beta-amyloid and tau PET signal processing and interpretation. The Data Management and Statistics Core will provide ongoing data management and analytical support.

Expected Results: The study will provide empirical evidence for race-specific differences in regional tau deposition and elucidating biological underpinnings for racial differences in risk of developing Alzheimer’s disease. The data will form the basis for an NIH R01 application. The findings will inform clinical interventions aimed at improving sleep as a therapeutic target for prevention of Alzheimer’s disease, especially in Black patients.

Project Title: In Vivo Characterization of Cortical Myelin Alterations in Aging Brain

Principal Investigator: Mariana Lazar, PhD, Associate Professor, Department of Radiology
Award Period: November 1, 2020–April 30, 2022

Project Rationale: The progression of Alzheimer’s disease follows a pattern similar to retrogenesis—the deterioration of functions in reverse order of their acquisition during development. This process is paralleled by neuropathological retrogenesis. White matter myelination, or the development of protective sheaths surrounding the axons (nerve fibers), is a prolonged process that continues into the middle age—and it is also affected early in Alzheimer’s disease. Intracortical myelin (ICM) is likely to affect cognitive functioning, but in vivo data on ICM are lacking. MRI techniques that probe the protons bound to macromolecules, which are primarily associated with myelin, may be employed to derive measures of ICM and yield early biomarkers of Alzheimer’s disease.

Project Aims: The overall goal of this project is to relate noninvasive measures of ICM to cognitive status. In a prospective study, quantitative magnetization transfer (qMT) and g-ratio imaging—a combination of qMT and diffusion imaging—will be performed to compare the ICM metrics in subjects with mild cognitive impairment, subjects with subjective cognitive decline, and healthy controls. A retrospective study of the Alzheimer’s Disease Research Center database will derive myelin metrics from the ratio of conventional T1-weighted to T2-weighted images. These metrics will be related to the verbal and visual working memory spans, cognitive functions that are affected early in Alzheimer’s disease, as well as biomarkers derived from cerebrospinal fluid and PET imaging.

Alzheimer’s Disease Research Center Resources Used: This project will prospectively enroll subjects recruited through our Clinical Core and retrospectively examine all Alzheimer’s Disease Research Center imaging data to evaluate progressive loss of myelin in vulnerable areas of the brain.

Expected Results: The project will identify noninvasive biomarkers of disease and response to treatment and indicate whether demyelination could be considered as a new treatment target, addressing the focus areas of the National Institute on Aging Alzheimer’s Disease and Alzheimer’s Disease Related Dementias Program.