Monthly Archives: March 2018

Genetic Evidence Suggests Iron is Linked to Alzheimer’s Disease

According to a recent study, people with a rare variant in the HFE gene are three times less likely to develop dementia than the general population.

You’ve probably heard that consuming enough iron is important for overall health. However, too much iron can also be a bad thing. In particular, people with Alzheimer’s disease often have abnormally high levels of iron in their brains. (See The Role of Metals in Alzheimer’s Disease). The question of whether iron is a cause or consequence in Alzheimer’s still remains unanswered.

In a paper published this week in PLoS One, a group of Italian researchers investigated whether the genes that control levels of iron in the body could be related to the risk of dementia. They recruited 765 subjects who had Alzheimer’s disease, vascular dementia, or mild cognitive impairment, as well as 1,086 healthy controls of a similar age. Then they took DNA samples from the subjects and looked at four different genes that are involved in iron metabolism.

They found that one gene called High Ferrum (HFE), which is responsible for controlling absorption of iron from the blood, was protective against dementia. Specifically, subjects who had a particular variant of the HFE gene were one-third as likely to develop Alzheimer’s disease or vascular dementia compared to subjects who didn’t have the protective variant. The effect was even stronger for mild cognitive impairment, which the HFE variant reduced the risk to only one-fifth.

The researchers then looked at another gene called APOE, which has previously been shown to be involved in Alzheimer’s disease. People with the APOE4 variant of this gene were more than four times as likely to have Alzheimer’s. However, in subjects who also possessed the protective HFE variant, the impact of APOE4 was completely attenuated, and their risk of Alzheimer’s was normal.

How could the HFE gene protect people from dementia? One possibility, known as the metal hypothesis of Alzheimer’s disease, suggests that iron makes amyloid-beta plaques more toxic. Amyloid-beta, a protein that accumulates in Alzheimer’s patients’ brains, can interact with various metal ions to become extra toxic. Normally metals are blocked from entering the brain by the blood-brain barrier, but this barrier tends to become leaky in older people. Thus the hypothesis suggests that influx of iron and other metals into the brain may cause amyloid-beta to aggregate and become more toxic, thus contributing to the development of Alzheimer’s.

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The metal hypothesis suggests that the toxicity of beta-amyloid could be increased when it binds to metal ions. Image Source

However, the metal hypothesis can’t entirely explain these recent findings. For one thing, the variants in iron-controlling genes were also protective against vascular dementia, which does not involve amyloid-beta. In addition, the researchers did not observe any differences in blood iron levels based on these genetic variants, so it’s unclear exactly how these genes may be affecting iron metabolism. Future studies are needed to clarify if and how iron could be involved in Alzheimer’s and other types of dementia.

 

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What is the difference between dementia and Alzheimer’s disease?

This is probably the most common question I’m asked by my readers, so I decided to devote an entire article to clearing up the confusion. Doctors and scientists often throw around words like “dementia,” “Alzheimer’s,” and “mild cognitive impairment” without making it clear what the difference is between them. Understanding what each of these terms mean is important for being able to interpret articles and recognize how scientific findings may apply to you.

Let’s start with dementia. Dementia itself is actually not a disease, but a set of symptoms. The most well-known dementia symptom is memory loss, but it also includes other things such as difficulty communicating, impaired attention, poor judgement, and a decline in visual perception.

Dementia symptoms can be caused by many different diseases. The most common cause of dementia is Alzheimer’s disease, which makes up around 60% of all dementias. However, many other diseases can cause dementia, including Parkinson’s disease, vascular dementia, frontotemporal dementia, and Lewy body disease. Dementia is often referred to as an “umbrella term” for a range of symptoms than can be caused by multiple diseases.

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Dementia is an “umbrella term” for a set of symptoms that can be caused by several different diseases. Image Source

I like to use an analogy to make this distinction a bit clearer. Think of Alzheimer’s disease like the flu. These are both diseases with a particular cause. Now think of some of the symptoms of having the flu: congestion, chills, nausea, and so on. There are many different diseases that can cause these symptoms, like a cold or sinus infection. In the same way, there are multiple diseases that can cause dementia symptoms.

To put it another way: everyone with Alzheimer’s disease has dementia, but not everyone with dementia has Alzheimer’s disease.

Now, there’s a third term you may have also heard thrown around: mild cognitive impairment, or MCI. It’s characterized by memory problems that are noticeable but not severe enough to interfere with daily life, such as forgetting appointments, losing your train of thought, and having trouble with planning or organization. Some people with MCI later progress to Alzheimer’s disease or other dementias, while others do not. Around 20% of adults over age 65 have MCI.

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Mild cognitive impairment sometimes progresses to Alzheimer’s disease or other dementia-causing diseases. Image Source

So there you have it! To summarize:

  • Dementia is a set of symptoms that include memory loss, impaired attention, and and poor judgement.
  • Alzheimer’s is one of several diseases that can lead to dementia symptoms.
  • Mild cognitive impairment is a less serious memory problem than can, but does not always, progress to dementia.

Hopefully that helps to clear up some of the confusion surrounding these three terms! As always, feel free to comment or send me a message if there are any other topics you’d like me to explain.

 

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