# In vivo MRI Biomarkers of Microstructural Correlates of Brain Pathology in Preclinical and Early Alzheimer Disease

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $548,454

## Abstract

This grant application addresses a significant health problem - Alzheimer’s disease (AD) - that affects ~5.3 million
people in the US and 20-30 million worldwide. As the population ages, these numbers are anticipated to rise,
stimulating an intense search for disease prevention and treatment therapies as well as for biomarkers allowing
early identification of AD. The latter is very important due to the existence of a long pre-symptomatic period that
can be used for the initiation of prevention trials of disease-modifying therapies in asymptomatic individuals, with
the goal of preventing cognitive decline as opposed to treating of symptoms that are already present.
 The main goal of this study is to provide a groundwork for using the innovative MRI-based Gradient Echo
Plural Contrast Imaging (GEPCI) technique for in vivo identifying early pathological changes in the AD brain.
This technique, GEPCI, developed in our laboratory, provides surrogates for quantitative assessments of
changes in the brain tissue structure at the cellular level and has been already successfully applied to evaluating
tissue damage in multiple sclerosis and some psychiatric diseases.
 Our preliminary data, obtained on well-characterized research participants recruited from studies of aging
and dementia at the Washington University Knight Alzheimer’s Disease Research Center, allowed us to
demonstrate for the first time that in vivo MRI-based measurements obtained on a clinical MRI scanner can
provide information on brain amyloid-β accumulation in human participants, and to distinguish between healthy
control, preclinical and mild AD stages. Based on these results, we plan to achieve the following Specific Aims:
1. Our Aim 1 is to develop a readily available, non-invasive quantitative in vivo MRI-based biomarker that can
serve as a surrogate for amyloid-β accumulation in the brain (a primary role of Aβ in the development of
Alzheimer's disease is now almost universally accepted).
2. Our Aim 2 is to establish specific quantitative and spatial patterns of GEPCI metrics abnormalities that would
distinguish between normal brain, preclinical AD, and very mild AD.
3. Our Aim 3 is to establish the effect of early AD-related brain tissue damage (defined by GEPCI surrogate
biomarkers) on cognitive performance and to test the hypothesis that the GEPCI metrics and/or changes in
GEPCI metrics can be predictors of the disease progression.
4. Our Aim 4 is to validate GEPCI measurements against direct neuropathology.
 The overarching goal of this proposal is to establish GEPCI as an in vivo non-invasive MRI technique
available in a conventional clinical setting for screening population for preclinical AD pathology and clinical drug
trials. GEPCI data are quantitative, reproducible and MRI scanner independent, thus allowing multi-center
applications. The non-invasive nature of our approach is especially important since most of currently available
biomarkers for identifying AD “are invasive, ...

## Key facts

- **NIH application ID:** 9908038
- **Project number:** 5R01AG054513-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** DMITRIY A YABLONSKIY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $548,454
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908038

## Citation

> US National Institutes of Health, RePORTER application 9908038, In vivo MRI Biomarkers of Microstructural Correlates of Brain Pathology in Preclinical and Early Alzheimer Disease (5R01AG054513-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9908038. Licensed CC0.

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