Iron and age: Brain analysis

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  • Published: Jan 15, 2014
  • Author: David Bradley
  • Channels: Atomic
thumbnail image: Iron and age: Brain analysis

Brain samples

Graphite furnace atomic absorption spectrometry after microwave-assisted acid digestion of post mortem brain samples finds a possible correlation with the iron levels in different regions of the brain and a diagnosis of Parkinson's or Alzheimer's disease.

Medical researchers have long suspected a link between the control of iron levels in different regions of the brain and neurodegenerative disease. Accumulation of the metal seems to be associated with ageing. Now, research reported in the Journal of Trace Elements in Medicine and Biology provides details of the post mortem analysis (using graphite furnace atomic absorption spectrometry after microwave-assisted acid digestion) of brain tissues to map a possible correlation of iron levels in fourteen brain regions and the development of Parkinson's and Alzheimer's disease.

Chronic and degenerative diseases are likely to be of increased incidence in coming years across the globe as more people survive the infectious and other diseases of youth. While it is well known that chronic neurodegenerative diseases, which often emerge in old age, are the product of many aetiological factors, natural ageing, genetic predisposition as well as environmental and other external factor influence the risk. Moreover, disturbances in iron and levels of other trace elements in the brain are the focus of much suspicion as a significant contributor to the development of such diseases. The known accumulation of iron in the nervous system of PD and AD patients has been under close scrutiny for some time.

Region-specific iron

Patrícia Ramos and Agostinho Almeida of Porto University, Agostinho Santos, Nair Rosas Pinto, Ricardo Mendes and Teresa Magalhães of the National Institute of Legal Medicine and Forensic Sciences, in Porto, Portugal, explain that a link between iron homeostasis in the brain and the development of neurodegenerative disease has been investigated extensively in recent years. Evidence is accumulating, they say, suggesting that as we age, iron levels are altered in specific regions of the brain in patients with such diseases.

They have used AAS to analyse iron content in 14 different parts of the brain - frontal cortex, superior and middle temporal, caudate nucleus, putamen, globus pallidus, cingulated gyrus, hippocampus, inferior parietal lobule, visual cortex of the occipital lobe, midbrain, pons (locus coeruleus), medulla and cerebellum (dentate nucleus)] from samples taken from adults aged 53 to 101 years old. None of the donors were known to have a history or evidence of neurodegenerative, neurological or psychiatric disorders. These 14 regions are those recommended by Paine and Lowe in "Approach to the post-mortem investigation of neurodegenerative diseases: from diagnosis to research" (Diagn Histopathol, 2011, 17, 211-216), as "the suggested regions to be sampled when a neurodegenerative disease is suspected."

Distribution, that's the name of the game

Their data suggest that iron distribution in the adult human brain is spread heterogeneously throughout the tissues. Higher levels were seen in the putamen and globus pallidus whereas lower concentrations were measured in the pons and medulla. That said, they found that the age of the donor made a significant contribution to iron levels. The "positive correlation between iron levels and age was most significant in the basal ganglia (caudate nucleus, putamen and globus pallidus), the team reports. They also compared the data from the age-matched control group and found that there were altered iron levels in particular regions in a patient with Parkinson's disease patient (the basal ganglia) and two patients with Alzheimer's disease (the hippocampus).

"This work provides a comprehensive and updated background for Fe levels in non-diseased human brains. It may be a significant contribution for defining 'normal' iron levels, which would allow future interpretations of results obtained in studies of patients affected by neurodegenerative disease," the team concludes. In addition, their study highlights the need for precision in terms of defining the age, disease state and brain regions studied in future investigations.

"Trace elements are important from both a physiological (Zn, Se, Fe, Cu…) or toxicological (Al, Hg, Pb…) point of view," Almeida told SpectroscopyNOW. "Imbalances in essential trace element levels are suspected of being involved in ageing, decline of brain functions and, eventually, neurodegenerative diseases. But the exact relevance is not known." He points out that a major question is regarding the homogeneity or heterogeneity of levels within the brain. Iron distribution is heterogeneous. Some areas have a higher Fe content, some have a lower content. "For us, this is a proof of the physiological importance of iron and its involvement in brain processes," he adds. Moreover, the question of what happens in normal, natural ageing is important too, do for instance trace elements accumulate or decrease in different brain regions?

The team has also done parallel work with calcium and magnesium and will soon report data on zinc, manganese and several other trace elements. Almeida points out that "the merits of the work is mainly from Patricia Ramos" and he and his colleagues at the National Institute of Legal Medicine and Forensic Sciences, specifically Agostinho Santos, have great pleasure in supporting her efforts.

Related Links

J Trace Elements Med Biol, 2014, 28, 13-17: "Iron levels in the human brain: A post-mortem study of anatomical region differences and age-related changes"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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