# Immune system supports brain function

> **NIH NIH R37** · WASHINGTON UNIVERSITY · 2021 · $546,730

## Abstract

Aging is associated with cognitive decline, which can manifest pathologically as age-related dementia. Aging is
also the major risk factor for the development of Alzheimer’s disease. There is currently no effective treatment
for age-associated dementia and no therapies for Alzheimer’s disease. Challenges associated with brain
disorders include a lack in understanding of the underlying mechanisms and poor accessibility of the brain due
to the blood-brain barrier. Over the last decade, we have been studying meningeal spaces and their relevance
to brain function. Our long-standing interest in the meninges and its role in brain function has led us to
characterize meningeal lymphatic vessels and to observe many intriguing changes in meningeal immunity with
age, and accordingly to raise the questions: are meningeal immune and lymphatic alterations relevant to age-
related cognitive decline? If so, could meningeal lymphatic vasculature or meningeal immunity be therapeutically
targeted to alleviate age-related dementia and/or Alzheimer’s disease? Here, we are proposing to test our overall
hypothesis, that age-related impairment in meningeal lymphatic function results in impaired meningeal blood
vasculature (presumably through build-up of waste products), collectively leading to abnormal meningeal
immunity, which subsequently results in age-associated impairment of cognitive function. We propose that
improving meningeal lymphatic function (or directly targeting the immune system and/or its soluble mediators)
may be a plausible therapeutic approach for age-associated cognitive decline. Three specific aims were
designed to elucidate the role of meningeal vasculature and immunity in age-associated cognitive decline,
dementia, and mouse models of Alzheimer’s disease using state-of-the-art imaging, surgical and
pharmacological techniques in mice, as well as a validation of select findings in human dura specimens from
fresh autopsies. Specific aim #1 will establish whether dysfunction of meningeal lymphatics may exacerbate the
aging phenotype of meningeal blood vasculature; specific aim #2 will define the changes occurring in meningeal
immune cells upon vascular dysfunction; specific aim #3 is a therapeutic aim wherein several approaches to
boost healthy meningeal immunity—and thus improve cognitive function—will be tested. Understanding how
meningeal vasculature and immunity are changing with age and in diseases, such as Alzheimer’s disease, has
broad implications in numerous neurological conditions associated with aging. Our findings, therefore, have
significant potential to uncover the etiology of and identify novel therapeutic targets for age-related dementia and
Alzheimer’s disease.
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## Key facts

- **NIH application ID:** 10246260
- **Project number:** 5R37AG034113-12
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Jonathan Kipnis
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $546,730
- **Award type:** 5
- **Project period:** 2010-05-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246260

## Citation

> US National Institutes of Health, RePORTER application 10246260, Immune system supports brain function (5R37AG034113-12). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10246260. Licensed CC0.

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