September 5, 2016

expert reaction to magnetite, air pollution and Alzheimer’s

A paper published in the journal PNAS has reported the identification of the mineral magnetite in human brains. The mineral has been implicated in negative health consequences and the authors suggest that the samples originate from air pollution.

Dr Joanna Collingwood, School of Engineering, University of Warwick, said:

“It is important that further research is undertaken to understand the health implications of these intriguing new findings. The authors suggest that the discovery may be relevant to Alzheimer’s disease. Although mishandled iron in the brain may contribute to the toxicity of the hallmark amyloid plaques in Alzheimer’s disease, there is not yet enough known to establish whether this external source of magnetite from air pollution may be a factor in the disease.

“Iron oxide nanoparticles are normally found throughout the body, including the brain, as they are the primary form of iron storage and essential for health. The magnetite particles described in this PNAS study are particles of iron oxide that have different properties to the iron oxide nanoparticles normally formed in the brain. Iron is essential to maintain a healthy brain, but it may be an important factor in Alzheimer’s disease because of the way that iron can interact with the protein found in the amyloid plaques. This interaction produces toxic free radicals that can contribute to the death of brain cells: magnetite and other types of iron oxide can form in the brain during this interaction. http://pubs.acs.org/doi/abs/10.1021/ic402406g

“This new PNAS study provides evidence that there are also magnetite particles in the brain that have come from air pollution rather than having formed within the brain. We do not yet know what impact these externally formed particles will have on chemical reactions in the brain.

“Nanoparticles from external sources are normally cleared to organs such as the liver, so it will be interesting to see if there is evidence for magnetite from air pollution entering via the lungs and accumulating in a number of organs, or whether this observation is unique to the brain.

“Likewise, if air pollution is a contributing factor to the development or progression of Alzheimer’s disease, we might expect to see a greater number of cases of the disease, or an earlier age of onset, in areas with high levels of pollution.

“This new research will hopefully ensure that subsequent studies are undertaken to tackle these important questions.”

Dr Neil Telling, Institute of Science and Technology in Medicine, Keele University, said:

“This paper presents evidence that microscopic iron oxide particles of a type known as magnetite, with properties matching those found in airborne pollution, can be found in the human brain. Previous studies have shown how magnetite might contribute to the cause and/or progression of Alzheimer’s disease, because of the way it can affect chemical reactions in the brain. However, this same chemical reactivity means that the surface of magnetite particles will change quickly when exposed to air, creating a non-toxic surface layer (an iron oxide known as maghemite). As the particles in this study are thought to come from airborne pollution, it would be expected that their surfaces will have already been converted to the non-toxic form.

“Therefore, on their own, these airborne particles might not be expected to be a significant source of damage due to chemical reactivity. However there is a possibility that in combination with other factors of Alzheimer’s disease, such as the build-up of the amyloid plaques in the brain, these particles could be involved in damaging chemical reactions.”

Prof. Anthony Seaton, Emeritus Professor of Environmental and Occupational Medicine, University of Aberdeen, said:

“A hypothetical explanation of why exposures to very low mass concentrations of air pollution particles are associated with adverse effects on organs other than the lung, most notably the heart, took account of the fact that most such particles are in the nanometre range and are present in vast numbers, the body’s defences reacting to them as though they were micro-organisims. Subsequent developments of nanotoxicology have pointed to the influence of particle surfaces and the presence of metals capable of initiating Fenton reactions. There is now considerable evidence relating air pollution to both acute heart attacks and long term risk of heart attack, on the basis of inflammation. More recently epidemiological studies have suggested that air pollution may also be a factor in cognitive decline in the elderly and in cognitive impairment in the young, while nanotoxicology has shown that these small particles may reach the brain through the olfactory nerves.

“Studies in Mexico City have hinted at an association between air pollution particles in the brain and Alzheimer’s disease. One of the authors of these studies has now collaborated with UK researchers in the present study of brains from Mexico and Manchester to show the presence of magnetite nanoparticles of exogenous origin, almost certainly derived from traffic-related pollution, suggesting that such particles may be a factor in initiating the processes that lead to dementia.

“This is an important study and adds to the body of evidence that the combustion products of fossil fuel have widespread toxic effects on our health. The solution to this (and to climate change) is literally in our own hands as we take hold of the steering wheel.”

Prof. Peter Dobson, Principal Fellow, Warwick Manufacturing Group, University of Warwick and Visiting Professor of Physics, King’s College London and Chair of the Steering Committee at University of Birmingham’s Facility for Environmental Nanoscience Analysis and Characterisation (FENAC) said:

How robust is this study?

“I believe it is robust and that it does add important ideas. Many of the particles in the paper that are spherical however do resemble those that are made by low temperature colloidal methods, so they could be formed in the body from iron ions. They have selected a few larger ones that do look as though they might have been made via a high temperature process. Other studies are also pointing to an external origin of the magnetite found in the brain, but I don’t think we can be absolutely certain yet.”

How good is the evidence that magnetite nanoparticles cause Alzheimer’s?

“There is growing evidence that magnetite nanoparticles in the brain might be associated with Alzheimer’s. What is still not certain is if these are the cause or possible effect of Alzheimer’s. There also seems to be a shortage of data from the brains of people not suffering from Alzheimer’s.”

How good is the evidence that magnetite nanoparticles are in our cities’ air?

“There is strong and growing evidence for this.”

Are the magnetite nanoparticles in sufficient volume in our air to cause Alzheimer’s?

“Possibly and a lot hinges on the pathway to get to the brain. The paper mentions entering the brain via the olfactory nerve (and they quote good references, but there are many others, and indeed people are now considering this as a route to introduce nanoparticles into the brain to treat brain disease). The olfactory route is a very credible and plausible route for nanoparticles to enter the brain.”

Where do magnetite nanoparticles come from?

“They quote possible sources in the paper, but the brake lining of vehicles is very likely the main origin along with particles released by rail travel.”

Is this a cause for concern and what proportion of Alzheimer’s is it likely to cause?

“I don’t think we can say yet if it causes Alzheimer’s, but it is a cause for concern more generally, because magnetite particles have been linked to other health problems such as cardiovascular disease and pulmonary diseases.”

How does the hazard of magnetite nanoparticles compare to other air pollution hazards?

“It has to be set alongside the others such as diesel soot, NOx, tyre wear dust etc… The latter is probably the worst and least studied. A lot of the vehicle and roadside particulates originate from both road and tyre wear and this is difficult to quantify.”

If this is a cause for concern then what needs to be done? Do policymakers and members of the public need to be concerned or is it currently just indicative of needing more attention by researchers?

“All such things should be of public concern, but not to be over-played. It does need the attention of public health policy and research funding, and it needs this rather urgently.”

Dr David Reynolds, Chief Scientific Officer, Alzheimer’s Research UK, said:

“Little is known about the role of magnetite nanoparticles in the brain and whether their magnetic properties influence brain function. It’s interesting to see further research investigating the presence of this mineral in the brain, but it’s too early to conclude that it may have a causal role in Alzheimer’s disease or any other brain disease.

“We know that air pollution can have a negative impact on certain aspects of human health, but we can’t conclude from this study that magnetite nanoparticles carried in air pollution are harmful to brain health. It’s important to continue to study the impact of lifestyle and environment on brain health, although age and genetic risk factors also play an important role in influencing a person’s risk of Alzheimer’s.”

Dr Jennifer Pocock, Senior Lecturer, Institute of Neurology, UCL, said:

“This is an interesting paper which certainly gives evidence that pollution-born magnetite can end up in the brain. However, I think any correlation with this and Alzheimer’s disease is weak; the authors admit that these particles would enter by the olfactory unit, but a damaged one is needed. How likely is this in the general population and does this correlate with the cases of Alzheimer’s disease linked to magnetite in the brain? Also from the graphs from Mexico (Fig S1 and Table S1) there is no information regarding neurological disease, whilst the data from the Manchester set is very small.

“There needs to be a better study carried out to correlate the magnetite concentrations of patients who lived primarily in a city, for example, compared with patients living in relatively unpolluted area and analyses of their Alzheimer’s disease brain pathology correlated with magnetite concentrations. The lack of controls in this study is also a problem.”

Dr. Wolfgang Kreyling, External Scientific Advisor and former coordinator of aerosol-related research within the Focus Network Nanoparticles and Health of the Helmholtz Zentrum Munchen (HMGU), said:

“The study presented in the upcoming PNAS publication is indeed of utmost importance since there are numerous hints and lots of speculations about the translocation and subsequent accumulation of man-made mineral nanoparticles (NP) in the brain. Indeed if NP would accumulate in the brain of continuously exposed inhabitants of highly air-polluted metropolitan areas over the years, inflammatory processes are likely to occur which may lead to various disease endpoints such as neurodegenerative diseases and cancer. Besides many other reasons, the difficulties of providing sufficient evidence of such NP transport into the brain and its quantification together with the induction of the disease are immense to overcome the methodological and scientific challenges of such an analysis.

“Reading the paper carefully it appeared to me that the analyses focus either on samples obtained from the Mexico City population and the other samples from a group of neurodegenerative patients in Manchester, UK. This by itself is providing some evidence for the conclusions tried to be drawn by the authors. However, such complex studies need to be supported by (1) additional investigations on specifically selected control groups in order to prove whether the presence of iron oxide NP in the brain sections of the patients is associated with the disease or not. Hence age-matched studies on subjects living in Manchester, UK, – which had died for other reasons – are missing. Therefore, the role of the identified rounded magnetic iron oxide NP in the brain of the Manchester patients and their disease is suggested but not identified. (2) the other part of the study shows that all the samples obtained from inhabitants of Mexico City contain rather high levels of rounded magnetic iron oxide NP. Whether the NP presence results from the high air pollution in Mexico City is likely but not proven since a matched control group from a less polluted area in Mexico is missing. In addition, the question remains open as to whether these rounded magnetic iron oxide NP in the brain of Mexico City inhabitants play any role on neurodegenerative diseases.

“In summary, the results of this study are (1) an important step on a better understanding of the role of magnetic iron oxide NP observed in the brain of patients with neurodegenerative diseases and (2) the Mexico City analysis indicates the likelihood of brain accumulation of iron oxide NP originating from air pollution. However, since the essential mechanistic links between both parts of the study are missing the search for causal evidences between air pollution and neurodegenerative diseases must go on.”

‘Magnetite pollution nanoparticles in the human brain’ by Maher et al. published in PNAS on Monday 5^th September. 

Declared interests

Prof. Seaton: “None to declare.”

Prof. Dobson: “I have no conflicts of interest.”

Dr Reynolds: “No conflict of interest.”

Dr Pocock: “No declaration of interest to make.”

Dr Kreyling: “None to declare”