# Hypertension, brain clearance and markers of neurodegeneration

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $737,322

## Abstract

PROJECT SUMMARY
 Age is the strongest risk factor for brain diseases related to accumulation of misfolded proteins and also
the risk for vascular diseases. So far, there is little evidence that excessive production of proteins forming brain
deposits in neurodegenerative conditions contributes to their pathology. A reduced clearance of brain waste
has emerged as a possible factor underlying disease development. Cerebral blood flow (CBF) and vascular
pulsations facilitate the passage of extracellular fluid through the brain, a channel for removing waste products.
We contend that both CBF and brain clearance depend on proper structure and health of brain vessels. Indeed
vascular conditions are significant risk factors for neurodegeneration.
 Although epidemiological studies point out to vascular disease as a major risk factor for dementia, and
corroborate related CBF reductions, there is no direct evidence in humans supporting the pathway:
vascular disease  hemodynamic impairment  clearance deficit  neurodegeneration
We propose to examine this pathway, using our newly developed Positron Emission Tomography (PET)-based
tool to estimate brain clearance. Over 5 years we will conduct a 24-month longitudinal study of 70 cognitively
healthy subjects 60-80 years old, classified at baseline into: 1) normotensive NT (n=20), 2) controlled
hypertension C-HTN (n=20), 3) Uncontrolled hypertension or Untreated hypertension UU-HTN (n=30). Our
goals are:
AIM1. To test the relationship between vascular disease (HTN), reduced CBF and impaired brain clearance
AIM2. To examine whether treatment of HTN restores CBF and improves brain clearance
AIM3. To tests whether HTN, CBF and brain clearance predict markers of neurodegeneration and cognitive
performance and whether clearance mediates the effects of HTN and CBF on these markers.
 We chose HTN since it is a common risk factor for neurodegenerative diseases. Our preliminary work
documented its association with hemodynamic deficits, and showed that with longitudinal reduction in blood
pressure these deficits may be reversible. As an index of neurodegeneration we will use cerebrospinal fluid t-
tau/aβ42 ratio (total tau/ amyloidβ-42) – a biomarker of Alzheimer's disease (AD). AD is by far the most
common age-related neurodegenerative disease and we have reported that higher vascular burden is related
to more abnormal AD biomarkers.
 This project will advance our understanding of how common vascular condition affects the brain and
facilitates neurodegeneration. Advanced imaging and analytical techniques implemented by an experienced
team with a long record of collaboration, permit a comprehensive and novel approach to essential questions.

## Key facts

- **NIH application ID:** 9998041
- **Project number:** 5R01NS104364-04
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Lidia Glodzik
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $737,322
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998041

## Citation

> US National Institutes of Health, RePORTER application 9998041, Hypertension, brain clearance and markers of neurodegeneration (5R01NS104364-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9998041. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*