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.

Keywords: Alzheimer’s disease; aging; iron; neurodegeneration.

Figure 1

Sketch of the coronal section of the brain where several structures belonging to basal ganglia are detailed. For putamen, globus pallidus, and caudate nucleus, the mean iron levels (in μg/g) reported by Ramos et al. [16] are given. The regions with the smallest value of deposited iron are filled in in blue, in red the highest ones are shown, and in violet the intermediate scores are given. The structures not analysed in detail are filled in in grey.

Figure 2

Comparison of the iron concentration estimated with QSM (susceptibility expressed in ppb, reported on the left-side scale, and interpolated by the green and blue curves) and post-mortem analysis (expressed in μg/g, reported on the right-side scale, and interpolated by the red curve) in three brain areas (putamen, caudate nucleus, and globus pallidus). On the x-axis, the age, in the range of 60–80 years, is reported [16,23,26].

Figure 3

Potential mechanisms involved in the modulation of the brain iron concentration during aging compared with those leading to neurodegeneration and AD. Differences in brain areas are already present in normal brains, but genetic factors, ferroptosis, microbleeds, and other alterations can shift the iron content values from what is expected in a normal aged brain to larger values (darker colours), predicting neurodegeneration.