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Center for Cognitive Health

Iron and Amyloid: Correlations to Entorhinal Cortex Degeneration

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       Research into the prevention and treatment of Alzheimer’s disease (AD) frequently starts small, with the discovery of risk factors that correlate with elevated deposition of AD biomarkers: amyloid (Aꞵ) plaques and neurofibrillary tangles (NFTs). Recently, researchers observed one such phenomenon involving the build-up of iron in the brain and the localization of Aꞵ.

       Firstly, it has been known that iron, a vital mineral in the body, has the capability to build up in the brain as we age. Normally, iron is bound in heme, a component of red blood cells, in order to aid in the binding of oxygen for distribution throughout the body. When there is too much iron in the body it forms iron deposits that can induce oxidative stress and cell damage. Furthermore, iron is also found within the molecules of Aꞵ and NFTs, and previous studies suggest iron deposits may encourage AD pathology.

       In the current study, researchers used Amyloid-PET and T2-weighted MRI imaging of 70 cognitively normal participants to measure cortical amyloid burden and non-heme iron deposited in the striatum of the brain. They did not find a direct correlation between amyloid burden and striatal iron concentration, and hypothesized this may be due to striatal iron deposition being limited until the later stages of AD. They did, however, notice that in cases of high amyloid and high striatal iron the entorhinal cortex degenerated in relation to age, while those with amyloid but low iron levels in the brain had larger entorhinal cortices suggesting reduced degeneration.

       The researchers hypothesized that reduced degeneration of the entorhinal cortex in the presence of amyloid but low iron might be due to amyloid plaques’ tendency to surround iron deposits, effectively protecting nearby brain regions from the negative impacts of iron deposits. Unfortunately, this protective effect doesn’t last with continued iron deposition having a negative impact on entorhinal cortex size.

       There are current and upcoming trials aimed at reducing/removing iron deposits prior to onset of neurodegeneration that show some promise as a preventative treatment. It is especially promising considering that the correlation between iron levels in the brain and entorhinal cortex degeneration were detectable even amongst non-impaired participants, suggesting that this method of treatment may work even in mildly symptomatic or even presymptomatic individuals, preventing brain volume loss before it has even begun!

Bilgel, M. & Bischof, G. N. Early role of iron in modulating amyloid’s association with neurodegeneration [Internet]. Neurology. 2020. Available from: https://n.neurology.org/content/95/18/809?sso=1&sso_redirect_count=1&oauth-code=BZ9uF6n9xCjHLHF8kd-f8zPfZ6Vgxd2gqxNz-SF3y2w