R01AG083874

Plasma brain-derived tau: A novel Alzheimer's disease-type neurodegeneration biomarker with potential to complete the AT(N) scheme in blood.

While the amyloid(A)/tau(T)/neurodegeneration(N) framework has been validated against neuropathology, cerebrospinal fluid (CSF), and neuroimaging biomarkers, its implementation in blood is incomplete. We now have high-performance plasma A and T markers that become abnormal according to AD pathophysiology.

However, the current N marker - neurofilament light (NFL) - is a non-disease-specific indicator of neurodegeneration/neuronal injury. Moreover, plasma total-tau (T-TAU) has large overlaps between diagnostic groups and does not correlate with CSF T-TAU.

We have developed and validated a novel AD-type neurodegeneration biomarker (referred to as brain-derived tau [BD-TAU]) with the capacity to complete the AT(N) framework in blood. Our overall goal is to perform a large-scale clinical and pathophysiological validation of plasma BD-TAU.

We will leverage five longitudinal, already existing, racially/ethnically diverse sporadic AD cohorts (N = 2,594) with clinical, in vivo, and post-mortem evaluations to answer the following specific aims:

AIM 1: To compare associations of plasma BD-TAU, NFL, and T-TAU with clinical diagnosis of AD and longitudinal cognitive change.

AIM 2: To compare AT(N) profiles and associations for plasma BD-TAU vs. NFL and T-TAU.

AIM 3: To compare the (added) diagnostic value of plasma BD-TAU vs. NFL and T-TAU for autopsy confirmation of AD.

Exploratory AIM 4: To compare performances of plasma BD-TAU vs. NFL and T-TAU in different racial/ethnic groups.

If proven, BD-TAU will complete the AT(N) scheme in blood, improving diagnostic and prognostic accuracies and confidence, as well as the prediction of longitudinal cognitive change that are directly translatable to anti-AD clinical trials.

University Of Pittsburgh - Of The Commonwealth System Of Higher Education

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]

Pittsburgh, Pennsylvania 152221808 United States

Single Zip Code

Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01 Clinical Trial Optional) (PAR-22-093)

Amendment Since initial award the total obligations have increased 124% from $5,794,471 to $12,972,426.