Quantitative Susceptibility Mapping in Alzheimer's Disease Demonstrates Iron Accumulation in Early Disease Stages

Non-Invasive Imaging Technique Shows Disruption of Iron Balance in a Critical Brain Region for Cognition

Reference:

Mohammadi S, Ghaderi S, Fatehi F. Iron accumulation/overload and Alzheimer's disease risk factors in the precuneus region: A comprehensive narrative review. Aging Med (Milton). 2024 Oct 22;7(5):649-667. doi: 10.1002/agm2.12363. PMID: 39507230; PMCID: PMC11535174.

Key Points:

• Iron overload in the body, which is often associated with conditions such as hereditary hemochromatosis or excessive iron intake, can cause a variety of problems such as oxidative stress, inflammation, and damage to cells and neurons.

• One aspect of Alzheimer’s Disease (AD) that has received increasing attention is the role of iron accumulation and dysregulation of iron homeostasis in the brain.

• Quantitative susceptibility mapping (QSM) is an MRI method that enables the measurement of materials that cause changes in susceptibility.

• Metal dyshomeostasis, intracellular iron deposition, and ferroptosis are key causes of neuronal loss in patients with AD.

• In the early stages of AD, amyloids tend to accumulate mainly in the temporal, basal frontal, and occipital lobes. As the disease advances, amyloid deposition spreads to other areas of the brain.

• Iron is found at high levels in plaques and can cause Aβ to aggregate, which is cytotoxic in vitro.

• Iron overload can also lead to autophagic cell death and ferroptosis as well as contribute to the phosphorylation of tau protein, leading to the formation of neurofibrillary tangles (NFTs), all of which increase the risk of NDD.

• Excessive iron accumulation in the brain can initiate a chemical reaction called the Fenton reaction, leading to increased oxidative stress, which is a hallmark of AD.

• Authors Conclude: Together, these findings suggest that iron accumulation, measurable through QSM, may accelerate pathogenesis in a sensitive hub region, contributing to downstream atrophy and cognitive deficits. As an early non‐invasive neuroimaging biomarker of iron burden and oxidative stress, QSM holds promise for improving early diagnosis, tracking disease stages, and monitoring therapeutic responses in AD and related dementias

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