RF1AG091421

THE INTERPLAY OF NEURONAL ACTIVITY AND SYNAPTIC ABNORMALITIES AND THEIR RESTORATION THROUGH MITOCHONDRIA IN ALZHEIMER'S DISEASE - SUMMARY ALZHEIMER'S DISEASE, A LEADING CAUSE OF DEMENTIA, IS CHARACTERIZED BY SYNAPTIC DYSFUNCTION AND ABERRANT NEURAL ACTIVITY CONTRIBUTING TO COGNITIVE DECLINE, WITH MITOCHONDRIA BEING AN EARLY TARGET OF AMYLOID PATHOLOGY. THIS SETS OFF A VICIOUS CYCLE INVOLVING SYNAPSES, NEURAL ACTIVITY, AND MITOCHONDRIA, WHICH MAY DIFFER DEPENDING ON AGE AND BRAIN REGION. THIS PROPOSAL SEEKS TO INVESTIGATE THE INTERCONNECTEDNESS OF THESE FACTORS IN AN AGE- DEPENDENT MANNER ACROSS MULTIPLE BRAIN REGIONS. BY UTILIZING MOUSE MODELS OF ALZHEIMER'S DISEASE, THE STUDY AIMS TO DETERMINE WHETHER MODULATION OF NEURAL ACTIVITY, SYNAPSES, OR MITOCHONDRIA COULD ENHANCE NEURAL PLASTICITY IN AMYLOIDOSIS. THROUGH A COMBINATION OF IN VIVO AND EX VIVO APPROACHES, THE PROPOSAL AIMS TO UNRAVEL THE RELATIONSHIP BETWEEN NEURAL ACTIVITY AND SYNAPTIC ABNORMALITIES AND TEST THE EFFICACY OF TARGETING CYCLOPHILIN D, A COMPONENT OF THE MITOCHONDRIAL MEMBRANE PERMEABILITY TRANSITION PORE, IN IMPROVING MITOCHONDRIAL HEALTH AND REVERSING SYNAPTIC AND NEURAL ACTIVITY DEFICITS.

University Of Kansas Center For Research

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]

Kansas United States

State-Wide

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