# Sleep-dependent modulation of cerebrospinal fluid flow in aging and across genetic risk for Alzheimers disease

> **NIH NIH R01** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2021 · $700,219

## Abstract

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.

## Key facts

- **NIH application ID:** 10099295
- **Project number:** 1R01AG070135-01
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Laura Diane Lewis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $700,219
- **Award type:** 1
- **Project period:** 2021-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10099295

## Citation

> US National Institutes of Health, RePORTER application 10099295, Sleep-dependent modulation of cerebrospinal fluid flow in aging and across genetic risk for Alzheimers disease (1R01AG070135-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10099295. Licensed CC0.

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