Iron levels hasten Alzheimer’s disease

Brain

Brain

High levels of iron in the brain could increase the risk of developing Alzheimer’s disease and hasten the cognitive decline that comes with it, new research suggests.

The results of the study, which tracked the brain degeneration of people with Alzheimer’s over a seven-year period, suggest it might be possible to halt the disease with drugs that reduce iron levels in the brain.

 “We think that iron is contributing to the disease progression of Alzheimer’s disease,” neuroscientist Scott Ayton, from the University of Melbourne in Australia, told Anna Salleh at ABC Science.

“This is strong evidence to base a clinical trial on lowering iron content in the brain to see if that would impart a cognitive benefit.”

Alzheimer’s is a devastating disease that researchers suspect “begins when two abnormal protein fragments, known as plaques and tangles, accumulate in the brain and start killing our brain cells,” explains Fiona Macdonald for ScienceAlert.

It starts by destroying the hippocampus – the region of the brain where memories are formed and stored – and eventually damages the region where language is processed, making it difficult for advanced Alzheimer’s patients to communication. As the disease’s gradual takeover continues, people lose the ability to regulate their emotions and behaviour, and to make sense of the world around them.

But previous studies have shown that people with Alzheimer’s disease also have elevated levels of brain iron, which may also be a risk factor for the disease.

“There has been debate for a long period of time whether this is important or whether it’s just a coincidence,” Ayton told ABC Science.

The long-term impact of elevated iron levels on the disease outcome has not been investigated, the researchers say.

So Ayton’s team decided to test this, examining the link between brain iron levels and cognitive decline in three groups of people over seven years. The participants included 91 people with normal cognition, 144 people with mild cognitive impairment, and 67 people with diagnosed Alzheimer’s disease.

At the beginning of the study, the researchers determined the patients’ brain iron levels by measuring the amount of ferritin in the cerebrospinal fluid around the brain. Ferritin is a protein that stores and releases iron.

The researchers did regular tests and MRI scans to track cognitive decline and changes in the brain over the study period.

They found that people with higher levels of ferritin – in all groups – had faster declines in cognitive abilities and accelerated shrinking of the hippocampus. Levels of ferritin were also a linked to a greater likelihood of people with mild cognitive impairment developing Alzheimer’s.

Their data contained some other interesting takeaways: The researchers found higher levels of ferritin corresponded to earlier ages for diagnoses – roughly three months for every 1 nanogram per millilitre increase.

They also found that people with the APOE-e4 gene variant, which is known to be the strongest genetic risk factor for the disease, had the highest levels of iron in their brains.

This suggests that APOE-e4 may be increasing Alzheimer’s disease risk by increasing iron levels in the brain, Ayton told ABC Science.

The researchers say their findings, which were published in the journal Nature Communications, justify the revival of clinical trials to explore drugs to target brain iron levels.

In a study carried out 24 years ago, a drug called deferiprone halved the rate of Alzheimer’s cognitive decline, Ayton told Clare Wilson at NewScientist. “Perhaps it’s time to refocus the field on looking at iron as a target.”

“Lowering CSF ferritin, as might be expected from a drug like deferiprone, could conceivably delay mild cognitive impairment conversion to Alzheimer’s disease by as much as three years,” the team wrote.

Protein Treatment Staves Off Alzheimer’s Disease Symptoms

Protein Treats Alzheimer’s Disease

Protein Treats Alzheimer’s Disease

Alzheimer’s disease is the sixth leading cause of death in the United States, with over 1,200 individuals developing the disease every day. A new paper in the Journal of Neuroscience from lead author Dena Dubal of the University of California, San Francisco describes how manipulating levels of a protein associated with memory can stave off Alzheimer’s symptoms, even in the presence of the disease-causing toxins.

Klotho is a transmembrane protein associated with longevity. The body makes less of this protein over time, and low levels of klotho is connected to a number of diseases including osteoporosis, heart disease, increased risk of stroke, and decreased cognitive function. These factors lead to diminished quality of life and even early death.

Previous research has shown that increasing klotho levels in healthy mice leads to increased cognitive function. This current paper from Dubal’s team builds on that research by increasing klotho in mice who are also expressing large amounts of amyloid-beta and tau, proteins that are associated with the onset of Alzheimer’s disease. Remarkably, even with high levels of these toxic, disease-causing proteins, the mice with elevated klotho levels were able to retain their cognitive function.

“It’s remarkable that we can improve cognition in a diseased brain despite the fact that it’s riddled with toxins,” Dubal said in a press release. “In addition to making healthy mice smarter, we can make the brain resistant to Alzheimer-related toxicity. Without having to target the complex disease itself, we can provide greater resilience and boost brain functions.”

The mechanism behind this cognitive preservation appears to be klotho interacting with a glutamate receptor called NMDA, which is critically important to synaptic transmission, thus influencing learning, memory, and executive function. Alzheimer’s disease typically damages these receptors, but the mice with elevated klotho were able to retain both NMDA function and cognition. Part of the success also appears to be due to the preservation of the NMDA subunit GluN2B, which existed in significantly larger numbers than the control mice. The mechanism and the results of this study will need to be investigated further before developing it into a possible treatment for humans in the future.

“The next step will be to identify and test drugs that can elevate klotho or mimic its effects on the brain,” added senior author Lennart Mucke from Gladstone Institutes. “We are encouraged in this regard by the strong similarities we found between klotho’s effects in humans and mice in our earlier study. We think this provides good support for pursuing klotho as a potential drug target to treat cognitive disorders in humans, including Alzheimer’s disease.”

 

Source:  iflscience.com

Alzheimer’s as Type 3 diabetes

Alzheimer’s could be reclassified as Type 3 diabetes:
Alzheimer's could be reclassified as Type 3 diabetes

Alzheimer’s could be reclassified as Type 3 diabetes

Growing evidence that Alzheimer’s is primarily a metabolic disease has led some researchers to propose reclassifying it as Type 3 diabetes, according to the Guardian. Such a revelation could have profound implications on the role that the junk food industry plays in causing Alzheimer’s. Today an estimated 35 million people suffer from Alzheimer’s disease around the world, and as many as 346 million people suffer from diabetes. Both numbers are expected to rise exponentially over the next several decades — rises that also happen to be correlated with increasing obesity rates. The correlation is so uncanny that many scientists are investigating a causal relationship between all three epidemics, with staggering results. Type 2 diabetes has already been strongly linked with obesity and diet as well as with dementia and Alzheimer’s. For instance, Type 2 sufferers are two to three times more likely to get Alzheimer’s than the general population. The link between Alzheimer’s and obesity has been studied less, but a growing cacophony of research is filling that gap. For instance, studies have strongly linked midlife obesity to Alzheimer’s. Fitness and a better diet have also been linked to a decreased occurrence of dementia. Now new studies are suggesting a link even more profound: that Alzheimer’s may be caused directly by the brain’s impaired response to insulin. A 2005 report found that levels of both insulin and insulin-like growth factors in the brains of Alzheimer’s patients were lower than normal, with the lowest levels being found in the brain regions most devastated by the disease. Meanwhile, a report released just last year found that an insulin spray helped improve memory skills in people with Alzheimer’s. Insulin has a well-defined role in the brain’s chemistry. It helps regulate the transmission of signals between neurons. It’s not difficult to begin connecting the dots at this point. A causal relationship between Alzheimer’s and the brain’s insulin regulation isn’t difficult to imagine and detail. Of course, more research needs to be done to know for sure, but if Alzheimer’s and other kinds of dementia are proven to be another form of diabetes, then the obesity epidemic — and the junk food industry that fuels it — could have consequences on public health that are even more profound than previously realized.