R01AG070135

Sleep-Dependent Modulation of Cerebrospinal Fluid Flow in Aging and across Genetic Risk for Alzheimer's Disease - Project Abstract

Sleep is essential for brain health, and neurodegenerative diseases are associated with substantial sleep disruptions. Disrupted sleep is now thought to not just be a symptom of neurodegeneration, but potentially to also contribute to the onset of the disease. Notably, Alzheimer's disease pathology is associated with loss of EEG slow waves during non-rapid eye movement (NREM) sleep. Sleep is thought to be important for clearance of proteins such as amyloid-beta and tau from the brain into the cerebrospinal fluid (CSF), and the human brain exhibits waves of CSF flow during NREM sleep, suggesting that CSF flow during sleep may play a role in its effects on brain health.

This proposal aims to understand the link between neural slow waves during sleep and CSF flow in healthy aging and in individuals at risk for Alzheimer's disease. We hypothesize that neural activity can induce CSF flow through its effects on cerebral blood volume. We, in turn, predict that loss of neural slow waves during sleep in the aging brain may lead to loss of sleep-dependent CSF flow, and that this decline is associated with Alzheimer's disease genetic risk factors.

To test our hypothesis, we will use multimodal imaging to simultaneously measure neural activity, hemodynamics, and CSF flow. We will test the link between neural activity and CSF flow and will identify whether the decline in sleep slow waves in older adults is associated with less CSF flow. We will further examine whether this process is more severely disrupted in healthy older adults with genetic risk for Alzheimer's disease.

Together, these studies will establish a biological mechanism for how altered sleep in aging leads to altered fluid flow dynamics, and this knowledge will form an essential foundation for the development of future biomarkers and interventions to evaluate and modulate CSF flow in the aging brain.

Massachusetts Institute Of Technology

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]

Cambridge, Massachusetts 021394301 United States

Single Zip Code

Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-19-056)

Amendment Since initial award the total obligations have increased 370% from $700,219 to $3,292,586.