New Research: Can lead and manganese in blood identify Alzheimer’s disease?

Unfortunately not.

Lead has been in the news a lot recently; you’d have to be hiding under a rock to not know about the current environmental tragedy happening in Flint, Michigan, where toxic levels of lead have been found in the municipal water supply.

Although lead as many practical uses, it’s probably just as famous as being extremely poisonous. Similarly, manganese, which unlike lead actually has an essential role in normal physiology, is also toxic when present at high levels. In an upcoming special issue on the neurotoxicity of lead, manganese and mercury in Ferrumblogger’s favourite journal Metallomics (you can access the article for free here), we’ve just published findings from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing, one of the world’s largest group of Alzheimer’s disease patients, looking at whether lead and manganese in blood can be used to predict the disease.

Measuring lead isn’t easy. It’s incredibly toxic even at low levels, and even with the most sensitive analytical techniques it’s hard to get accurate readings. AIBL has over 1,000 participants, and we measured lead and manganese in both serum and red blood cells in each individual. Using some nifty statistics from Dr Noel Faux, who works for IBM and is an ex-researcher (and honorary Fellow) at the Florey Institute, we were able to decipher the tiny levels of lead in serum to see if lead levels in blood were associated with either Alzheimer’s disease of a condition called ‘mild cognitive impairment’, or MCI, which is generally thought to be a posFigure 1 - Serum Pbsible prelude to AD. An interesting feature we found was that lead levels, independent of disease status, varied depending on where the samples were collected (AIBL has sites in Perth and Melbourne), and age, which isn’t entirely unexpected for an environmental toxin that a) both accumulates with age, and b) is found at different levels depending where in Australia you live. After correcting for these variables, we found that no relationship between disease status and lead levels was present in the 1,000 strong AIBL cohort (see the figure to the left).

Where things did change according to disease was the amount of manganese in serum. Here, manganese actually decreased in AD patients after correcting for variation between sex and collection site (see the figure on theFigure 2 - Serum Mn.png right). As interesting as this is, the difference wasn’t really big enough to give us much confidence that we can use it in the future as some kind of marker of AD risk, particularly as MCI patients didn’t show a difference compared to healthy controls, suggesting that this change isn’t a gradual process.

In our search for a biomarker of AD that allows us to identify the disease is occurring long before symptoms become unmanageable, this fact tends to suggest that metal levels alone are not a useful tool for assessing AD risk. One of the other difficulties is interpreting levels of metals like lead in blood and relating it to the actual burden of the metal in the body. Over 90% of lead you’re exposed to is stored in your bones, where it is locked up and generally not toxic, but it is easily ‘remobilised’; that is, it can be released into the bloodstream and exert it’s toxic effects over a longer period of time. It’s estimated that circulating lead only provides a window of around 30 days, so using this approach for assessing the long term effects of lead toxicity might not have much use for studying chronic diseases like AD.

So, you might ask, why bother publishing negative data? It’s a question many scientists face, and something that can be very frustrating when scientific journals only want to print what they think are new and exciting discoveries. In many ways, reporting something that didn’t happen can be just as important, as it can help guide other scientists away from going down a particular road that can cost a lot of both time and money. Also, just looking at lead in blood doesn’t mean it’s not involved in AD, just that the information it provides might not be helpful in the long run.

For the people of Flint, the long term effects of their exposure to lead extend well beyond just risk of diseases like AD. Scientists will focus on the population of this beleaguered town for decades to come (rightfully so), and so should the policy makers that made the decisions that put them unwittingly in this position in the first place. Every piece of information about lead toxicity is more and more important to them now.

 

Posted in Irons in the fire: News from our lab

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