# Imaging brain fluid dynamics in relation to reactive astrogliosis and cerebral amyloid accumulation

> **NIH AG P01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2026 · $591,741

## Abstract

Project 3 Abstract
Intriguing evidence implicates reactive astrogliosis as impairing brain fluid dynamics (BFD) via multiple
mechanisms, including 1) altering expression of the aquaporin-4 (AQP-4) water channel along the astrocytic end
feet which line perivascular spaces and 2) modifying cerebrovascular vasomotion, a likely driver of perivascular
fluid flow. In turn, impaired BFD may lead to reduced clearance of β-amyloid (Aβ), resulting in aggregation and
Aβ plaque deposition. However, the temporal order of reactive astrogliosis, altered AQP-4 expression, impaired
BFD, and Aβ deposition along the aging and Alzheimer’s disease (AD) pathophysiological spectrum is not well
understood. These relationships and mechanisms, particularly the pathways from reactive astrogliosis to
impaired BFD and from impaired BFD to Aβ deposition, remain largely unexamined in vivo in humans. Our
preliminary data examining PET ventricular CSF efflux suggest that BFD are impaired early in the
pathophysiological spectrum, prior to cognitive decline, and are associated with Aβ deposition. These findings
together with growing evidence from animal model and postmortem studies lead us to believe that in vivo
neuroimaging markers of impaired BFD and reactive astrogliosis can predict future Aβ deposition. In order to
test this overall hypothesis and achieve the proposed aims, we will examine (1) brain fluid pulsatility over the
whole head at cardiac, respiratory, and vasomotion frequencies using a novel 7T MRI fast echo-planar imaging
(EPI) sequence; (2) ventricular CSF efflux using the Aβ PET tracer 11C-PiB; (3) enlarged perivascular space
morphology, potentially indicative of impaired BFD, using 7T MRI T1, T2, and FLAIR sequences; (4) reactive
astrogliosis using the novel monoamine oxidase B (MAO-B) PET tracer 18F-SMBT-1; and (5) Aβ deposition using
11C-PiB in a cohort of n=300 older adults (age 55 and older; 10% AD). With this data, we will perform a highly
innovative and comprehensive multimod

## Key facts

- **NIH application ID:** 11078801
- **Project number:** 5P01AG025204-19
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** HOWARD J AIZENSTEIN
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** AG
- **Fiscal year:** 2026
- **Award amount:** $591,741
- **Award type:** 5
- **Project period:** 2004-12-01T00:00:00 → 2028-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11078801

## Citation

> US National Institutes of Health, RePORTER application 11078801, Imaging brain fluid dynamics in relation to reactive astrogliosis and cerebral amyloid accumulation (5P01AG025204-19). Retrieved via AI Analytics 2026-05-18 from https://api.ai-analytics.org/grant/nih/11078801. Licensed CC0.

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