R01AG061900

BLOOD AMYLOID, TAU, AND NEURODEGENERATION BIOMARKERS AND PREDICTION OF CLINICAL ONSET, COGNITIVE DECLINE, AND DEMENTIA DIAGNOSIS - PROJECT SUMMARY IN ORDER TO ACCELERATE OBSERVATIONAL CLINICAL STUDIES AND TRIALS AND TO IDENTIFY APPROPRIATE PATIENTS FOR TREATMENTS, HIGHLY ACCURATE AND ACCESSIBLE DIAGNOSTIC TESTS FOR ALZHEIMER'S DISEASE (AD) ARE NEEDED. CLINICAL ASSESSMENTS ALONE ARE INSUFFICIENT FOR ACCURATE DIAGNOSES, AND THE CURRENT GOLD STANDARD TESTS FOR AD (CSF AND PET) ARE COSTLY, LIMITED TO SPECIALIZED MEDICAL CENTERS, AND PERCEIVED TO BE INVASIVE. IN OUR ONGOING PROSPECTIVE STUDY TO EVALUATE AMYLOID IN BLOOD AND IMAGING RELATED TO DEMENTIA (SEABIRD), WE DISCOVERED THAT DECREASED BLOOD PLASMA AΒ42/40 RATIO IS AN ACCURATE BIOMARKER OF AMYLOID PLAQUES AND CONFIRMED THIS IN A DIVERSE COMMUNITY- BASED POPULATION, ALSO DEMONSTRATING THAT BLOOD TESTS ARE FEASIBLE TO SCREEN THE GENERAL POPULATION. WE HAVE DISCOVERED AND REPORTED THE MOST ACCURATE AΒ42/40 AND PHOSPHORYLATED-TAU BLOOD BIOMARKERS (%PTAU217, %PTAU205, AND %PTAU181) AND DISCOVERED NOVEL FORMS OF NEUROFILAMENT LIGHT (NFL) THAT PROMISE TO QUANTIFY THE MAJOR DOMAINS OF AD PATHOPHYSIOLOGY. WITH DEMONSTRATION THAT REMOVAL OF AMYLOID PLAQUES LEADS TO DISEASE-MODIFYING TREATMENT CLINICAL BENEFITS, ACCESS TO ANTI-AMYLOID THERAPIES WILL DEPEND ON ACCURATE DIAGNOSIS, AND BLOOD BIOMARKERS WILL BE CRITICAL TOOLS FOR DOCTORS AND PATIENTS IN UNDERREPRESENTED POPULATIONS. HOWEVER, THERE ARE MULTIPLE QUESTIONS THAT NEED TO BE ADDRESSED TO INFORM ABOUT THE BIOLOGY, USE, AND INDICATIONS OF THESE RAPIDLY DEVELOPING AND UTILIZED BLOOD-BASED BIOMARKERS. THESE QUESTIONS INCLUDE: `WHAT ARE THE DIAGNOSTIC AND PROGNOSTIC PROPERTIES OF BLOOD AΒ, TAU, AND NEURODEGENERATION (A/T/N) BIOMARKERS TO MEASURE AMYLOID AND TAU PATHOLOGY, CLINICAL COGNITIVE DECLINE, AND DIAGNOSIS IN A REAL-WORLD CLINICAL PATIENT POPULATION?', AND `WHICH DEMOGRAPHIC, CLINICAL, OR GENETIC FACTORS INFLUENCE THE RELATIONSHIP OF BLOOD A/T/N BIOMARKERS TO THE GOLD STANDARDS OF CLINICAL COGNITIVE DECLINE, DEMENTIA, AND PET TESTS OF PATHOLOGY?' OUR PROPOSED STUDY, CALLED SUNBIRD (STUDY TO UNDERSTAND NOVEL BIOMARKERS IN RESEARCHING DEMENTIA), WILL ENROLL 1000 NEW PARTICIPANTS FROM PRIMARY AND SPECIALTY CARE CLINICS AND FOLLOW THE EXISTING ~1000 SEABIRD PARTICIPANTS. WE WILL INCORPORATE HIGH PERFORMANCE BLOOD-BASED BIOMARKERS TRACKING AMYLOID, TAU AND NEURODEGENERATION AND ASSESS THEIR RELATIONSHIP WITH TAU PET, AMYLOID PET, AND OTHER CLINICAL AD TESTS. WE WILL FOLLOW THESE COHORTS LONGITUDINALLY USING BLOOD SAMPLES, EHR DATA, AND IN-PERSON AND REMOTE COGNITIVE TESTING. WE AIM TO UNDERSTAND HOW BLOOD-BASED BIOMARKERS CAN IDENTIFY THOSE WITH CLINICAL SYMPTOMS DUE TO AD PATHOLOGY, DETERMINE IF BLOOD-BASED BIOMARKERS CAN BE UTILIZED IN LIEU OF PET OR CSF MEASURES, AND ALSO DIAGNOSE AND STAGE PATIENTS TO ENABLE TREATMENT AND PREVENTION IN THE CLINIC. THE PROPOSED WORK BUILDS ON THE PRIOR PIONEERING APPROACH THAT DISCOVERED AND VALIDATED BLOOD AMYLOID BIOMARKERS, DISCOVERED NOVEL TAU PHOSPHORYLATION SITES. THESE STUDIES WILL LAY THE GROUNDWORK FOR RAPID DEPLOYMENT TO ACCELERATE ENROLLMENT OF AD TRIALS, CLINICAL DIAGNOSIS, AND EARLY AND ACCURATE DIAGNOSIS FOR THE WHOLE POPULATION.

Washington University

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]

Saint Louis, Missouri 631101010 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 105% from $5,175,354 to $10,586,526.