# Quantitative Susceptibility Mapping (QSM) as a Non-Invasive Imaging Biomarker for Predicting Neurodegeneration in Alzheimer's Disease

> **NIH NIH R21** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $466,125

## Abstract

The long term objective of our research is to establish quantitative susceptibility mapping (QSM) as a
noninvasive MRI marker for predicting neurodegeneration in Alzheimer’s disease (AD). Our scientific premise
is that QSM can measure iron overload involved in AD progression. Our approach is to establish QSM as an
MRI marker for predicting neurodegeneration ex vivo using AD brain tissue pathology and in vivo by correlating
QSM with neurodegeneration measured on structural and metabolic MRI. The current AD research framework
is termed AT(N): the pathological presence of amyloid-beta (Aβ) plaques (A) and phosphorylated tau
neurofibrillary tangles (T) in the cortex and hippocampus cause neurodegeneration (N). However, tau tangles
exist without Aβ plaques, and Aβ plaques are found in healthy elderly controls. Therapies targeting Aβ
removed plaques but failed to improve cognition, suggesting that other contributors to neurodegeneration and
cognitive decline in AD should be examined. Therefore, there is a need to expand the AT(N) framework to
include new biomarker X or ATX(N). Iron is a candidate biomarker for AD. Iron is elevated in brains with clinical
AD and predicts cognitive decline. Iron deposition appears before structural/metabolic changes on MRI and on
metabolic PET. This promising prediction power of iron as a biomarker warrants further investigation for AD
patient management. Accordingly, we propose to establish QSM as a biomarker to predict disease progression
in AD. In this R21 project, we seek to obtain preliminary data through the following specific aims: Aim 1:
Establish the QSM cellular sources in AD brain tissue using immunohistochemical assays of iron, microglia,
Aβ, and tau, and using elemental iron measurements. Aim 2: Establish QSM as a biomarker that predicts
neurodegeneration measured on structural and metabolic MRI of subjects with Aβ pathology. This proposed
project is strongly supported by our experience and preliminary data, and its successful outcome will timely
establish QSM a quantitative biomarker for AD pathogenesis, progression, and treatment monitoring.

## Key facts

- **NIH application ID:** 10126496
- **Project number:** 1R21AG067466-01A1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Ilhami Kovanlikaya
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $466,125
- **Award type:** 1
- **Project period:** 2020-09-11 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10126496

## Citation

> US National Institutes of Health, RePORTER application 10126496, Quantitative Susceptibility Mapping (QSM) as a Non-Invasive Imaging Biomarker for Predicting Neurodegeneration in Alzheimer's Disease (1R21AG067466-01A1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10126496. Licensed CC0.

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