R01AG076153

Methods for Quantitative Neuroimaging of Tau Burden in Pre-symptomatic AD

Whereas amyloid deposition tends to occur broadly throughout cortical regions and with a relatively uniform pattern of progression over time, the distribution of tau is highly focal at the early stages of pathology. Its propagation to other regions demonstrates a more complex spatiotemporal evolution. In addition, the relatively lower abundance of tau in the brain compared to amyloid imparts greater requirements for binding affinity and selectivity of tau radiotracers.

Although second-generation tau tracers reported within the past few years appear to have more favorable properties in this regard, all tau tracers studied to date have been reported to exhibit off-target binding to various substrates. This can confound the quantification and interpretation of imaging data. The goal of this application is to develop innovative technologies that improve the quantification of tau PET imaging and enhance its utility in both research and eventual clinical settings.

To address the focal nature of tau deposition, especially at prodromal stages of the disease, we propose a novel kernel-based reconstruction method. This method uses structural MR images as prior information and incorporates motion correction to obtain images with unprecedented spatial resolution. This will allow for improved localization and quantification of tau in small structures such as the rhinal cortex and the locus coeruleus.

To mitigate the effects of off-target binding, we propose kinetic analysis strategies to identify non-specific, tau-specific, and off-target components. Additionally, we propose modeling tactics to estimate maps of cerebral perfusion. This will complement measures of tau burden as an additional index of brain function.

Lastly, we propose deep learning strategies to gain new insights into the spreading of tau and to predict this progression in individual subjects. These strategies will provide valuable information for understanding the pathophysiology of pre-symptomatic AD and potentially aid in early detection and intervention.

Yale Univ

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

New Haven, Connecticut 065103221 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 317% from $729,762 to $3,044,541.