Iron Deposition in Brain: Does Aging Matter?

Abstract

The alteration of iron homeostasis related to the aging process is responsible for increased iron levels, potentially leading to oxidative cellular damage. Iron is modulated in the Central Nervous System in a very sensitive manner and an abnormal accumulation of iron in the brain has been proposed as a biomarker of neurodegeneration. However, contrasting results have been presented regarding brain iron accumulation and the potential link with other factors during aging and neurodegeneration. Such uncertainties partly depend on the fact that different techniques can be used to estimate the distribution of iron in the brain, e.g., indirect (e.g., MRI) or direct (post-mortem estimation) approaches. Furthermore, recent evidence suggests that the propensity of brain cells to accumulate excessive iron as a function of aging largely depends on their anatomical location. This review aims to collect the available data on the association between iron concentration in the brain and aging, shedding light on potential mechanisms that may be helpful in the detection of physiological neurodegeneration processes and neurodegenerative diseases such as Alzheimer’s disease.

17β-oestradiol inhibits ferroptosis in the hippocampus by upregulating DHODH and further improves memory decline after ovariectomy

“…Many cellular and molecular events are shared between menopause and ageing, especially with respect to neurological functions. Among them are iron accumulation and subsequent mitochondrial dysfunction as well as the occurrence of neurodegenerative diseases [ 48 , 49 ]. For example, PD and AD have been reported [ 50 , 51 ].…”

Iron content affects age group differences in associative learning-related fMRI activity

“…Whereas comparable age effects were seen in the basal ganglia across metrics, the hippocampus showed a mixed pattern of both higher (R2 * ) and lower (QSM) iron in older than younger adults. Discrepancies in age differences in iron content have been reported between these approaches, at least for the globus pallidus (Betts et al, 2016;Ficiarà et al, 2022) and caudate (Li et al, 2014), which may reflect QSM being less sensitive than R2 * to factors other than iron that can also influence magnetic susceptibility (e.g., myelin, calcification, lesions; Barbosa et al, 2015;Betts et al, 2016;Parr et al, 2023). Regardless, QSM and R2 * are strongly correlated in iron-rich basal nuclei, as seen here and by others (Deistung et al, 2013;Li et al, 2014), supporting the notion that they provide complimentary information about iron content (Ficiarà et al, 2022), and which explains the highly similar pattern of results observed here across metrics.…”

“…Using these MRI approaches, more recent work confirms that iron content is highest in the basal ganglia relative to the hippocampus and cortex (Haacke et al, 2005), with smaller age group differences in the globus pallidus where iron content is high in both younger college-aged and older adults, but larger age group differences in the dorsal striatum where iron content is higher in older than younger adults (Cherubini et al, 2009;Ficiarà et al, 2022;Li et al, 2021;Pfefferbaum et al, 2009). This heterogeneity in iron distribution throughout the brain, as well as age-related variance in iron content, can produce testable hypotheses about the influence of iron on other neural substrates in aging.…”

“…Here, we took the opportunity to re-examine age group differences in learning-related BOLD within each region of interest, comparing effects before and after controlling for iron content. We first expected to replicate age group differences in iron content in the basal ganglia, but not the hippocampus (Cherubini et al, 2009;Ficiarà et al, 2022;Li et al, 2021;Pfefferbaum et al, 2009).…”

Dysfunctional Coupling of Cerebral Blood Flow and Susceptibility Value in the Bilateral Hippocampus is Associated with Cognitive Decline in Nondialysis Patients with CKD

“…27 Brain iron is not steady but dynamically increases or decreases. Overload regional iron deposition can damage neurons through induced oxidative stress products, A𝛽 plaques/tau deposition, promoting brain aging, 28 cognitive impairment, 29 and even Alzheimer disease. 30 Because of the regional inhomogeneity and magnetic properties of iron, different regions of brain tissue have different magnetic susceptibilities.…”