# Microglial, Inflammatory and Omics Markers of Cerebral Small Vessel Disease in the CHARGE Consortium

> **NIH NIH UH3** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2020 · $974,558

## Abstract

Cerebral Small Vessel Disease (SVD) is an important, potentially modifiable factor for clinical dementia.
 Recent data suggest that the age-specific incidence of dementia may be decreasing, partly as a result of better
management of vascular risk factors, lending urgency to dementia prevention trials but a major impediment is
the absence of circulating biomarkers for tracking onset and progression of SVD. Brain MRI imaging markers
 are the current gold standard for SVD but are too expensive and burdensome for repeated assessments.
Recent genetic studies, including from the Cohorts for Heart & Aging Research in Genomic Epidemiology
(CHARGE) consortium, implicate microglial inflammation and astroglia in the biology of SVD and dementia.
We propose to measure 2 circulating biomarkers of microglial inflammation (sCD-14 and YKL-40) and a
marker of astroglial injury (GFAP) in ~17,000 persons (including 4000 minority participants, 6000 with >2
MRI) across 5 CHARGE population-based cohorts.
 Specifcally, we will (1) examine the association of the novel biomarkers with (a) previously collected
MRI-defined SVD (white matter hyperintensities, lacunar infarcts and cerebral microbleeds), and in persons
under age 70, sensitive MRI measures of early, preclinical SVD such as fractional anisotropy on diffusion-
weighted imaging, regional cortical thinning and perivascular spaces; (b) previously collected measures of
cognitive function; and (c) neurocognitive and vascular consequences of SVD (dementia and stroke).
We will use a Mendelian Randomization framework and existing genetic data to examine causal relationships
between the novel biomarkers and MRI, neurocognitive, and clinical outcomes.
 (2) We will assess the incremental predictive utility of the novel biomarkers over (a) vascular risk
factor profiles such as the Framingham Stroke Risk Prediction score; (b) over a panel of previously measured
`candidate' biomarkers for SVD including CRP, IL6, TNF-alpha, fibrinogen, BNP, urine albumin, tHcy, ST2,
GDF15, TnI, BDNF, VEGF, MMP-9, beta-amyloid, clusterin and APOE and (c) we will identify a parsimonious
 set of biomarkers that best predict presence of SVD and risk of cognitive decline, stroke and dementia.
 In summary we propose to leverage extensive available data to identify and validate a novel
circulating biomarker profile of glial cell dysfunction that will improve our understanding of SVD biology and
help in the prediction of SVD and its associated adverse neurological outcomes.

## Key facts

- **NIH application ID:** 10003420
- **Project number:** 5UH3NS100605-05
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** MYRIAM FORNAGE
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $974,558
- **Award type:** 5
- **Project period:** 2016-09-30 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003420

## Citation

> US National Institutes of Health, RePORTER application 10003420, Microglial, Inflammatory and Omics Markers of Cerebral Small Vessel Disease in the CHARGE Consortium (5UH3NS100605-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10003420. Licensed CC0.

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