by In a big new finding almost a decade in the making, researchers from the Harvard Medical School say that they have found a key that can unlock many of the mysteries of Alzheimer’s disease and brain aging of the brain – the modest metal lithium.
Lithium is best known for medicine as a mood stabilizer given to people who have a bipolar disorder and depression. It was approved by the American Food and Drug Administration in 1970, but it was used by doctors to treat mood disorders in advance.
Now, researchers have shown for the first time that lithium is naturally present in small quantities in the body and that cells require that it functions normally – just like vitamin C or iron. It also seems to play a crucial role in maintaining the health of the brain.
In a series of experiments that reported in the journal Nature on Wednesday, researchers from Harvard and Rush -Universities discovered that exhausting lithium into the diet of normal mice ensured that their brains develop inflammation and changes related to accelerated aging.
For mice that were specially bred to develop the same types of brain changes as people with Alzheimer’s disease, a diet with a low lithium has the structure of sticky proteins that form plaques and tangles in the brain’s brains that are characteristics of the disease. The accelerated also memory loss.
Maintaining normal lithium levels in mice as they grew older, however, they protected against brain changes associated with Alzheimer’s.
If further research supports the findings, this can open the door for new treatments and diagnostic tests for Alzheimer’s, which affects an estimated 6.7 million older adults in the United States, according to the US CENTERS for Disease Control and Prevention.
An unprotective theory of Alzheimer’s disease
The research offers an unknown theory that helps to explain so much of the puzzle pieces that scientists have been trying to fit together for decades.
“It is a potential candidate for a common mechanism that leads to the multisystem degeneration of the brain that precedes dementia,” said Dr. Bruce Yankner, a professor in genetics at the Harvard Medical School, who led the study. “It will cost much more science to determine whether this is a common path … or one of the different paths,” to Alzheimer’s, he added. “The data is very intriguing.”
In a main article published in Nature, Dr. said Ashley Bush, a neuroscientist who leads the Melbourne Dementia Research Center at the University of Melbourne in Australia, that the researchers present “compelling evidence that lithium actually has a physiological role and that normal aging can hinder the regulation of the lithium level in the brain.” He was not involved in the study.
Nauw onderzoek van hersenweefsels voor menselijke en dieren, samen met genetische onderzoeken in de studie, vond het mechanisme dat lijkt te spelen: bèta -amyloïde plaques – de plakkerige afzettingen die de hersenen van de patiënten van Alzheimer omhullen – binden aan het lithium en het vasthouden aan lithium en het vasthouden aan lithium en het vasthouden, inclusief het type dat normaal aanwezig is in het lichaam, evenals de algemeen voorgeschreven Form. This binding exhausting lithium available for cells in the neighborhood, including important scavengers that are known as microglia.
When the brain is healthy and normal functioning, microglia are waste managers, who can clear beta -Amyloid before it can gather and cause damage. In the experiments of the team, microglia from the brain of lithium-deficient mice showed a reduced ability to wipe and break down beta-amyloid.
Yankner believes that this creates a downward spiral. The accumulation of beta -amyloid increases more and more lithium, so that the ability of the brain to erase it further paralyzes.
He and his colleagues tested different lithium compounds and found a – lithium orotate – that does not bind to amyloid beta.
When they gave lithium orotate to mice with signs of Alzheimer’s in their brains, these changes could be reduced: Beta amyloid plaques and tangles of Tau that stitched the memory centers of the brain were reduced. Mice treated with lithium could re -navigate and learn to identify new objects, while those who received placebos showed no change in their memory and thinking shortages.
Don’t try this at home
In its natural form, lithium is an element, a soft, silvery white metal that easily combines with other elements to form connections and salts. It is naturally present in the environment, also in food and water.
Lithium is a soft, silvery white metal that is naturally present in food and water. – Carla Gottgens/Bloomberg/Getty
Scientists have never fully known how it works to improve the mood – only that it does. The original formula for 7UP soft drinks included lithium – it was called 7UP litdoosoda – and was taught as a hangover curation and mood lifter “for hospital or home use.” Some hot springs that are known to contain mineral water were searched with lithium for wellness destinations for their curative forces.
Yet people who take doses of lithium on prescription – who were much higher than the doses used in the new study – can sometimes develop thyroid or kidney toxicity.
Tests of the mice that received low doses of lithium orotate did not show any signs of damage.
That is encouraging, Yankner said, but it does not mean that people have to try to take lithium supplements themselves.
“A mouse is not a one. Nobody is allowed to take anything alone based on mouse studies,” said Yankner.
“The lithium treatment data we have are in mice and it must be replicated in people. We have to find the right dose in people,” he added.
The normal amounts of lithium in our body and the concentrations given to the mice are small – about 1,000 times lower than doses that are given to treat a bipolar disorder, Yankner notes.
Yankner said he hoped that toxicity strives of lithium salts would start soon. Neither he nor one of his co-authors have a financial interest in the outcome of the investigation, he said.
The National Institutes of Health was the most important financier of the study, together with subsidies from private foundations.
“NIH support was absolutely crucial for this work,” said Yankner.
Proof builds up for the role of lithium in aging
The new research confirms earlier studies and hinted that lithium can be important for Alzheimer’s. A large Danish study published in 2017 discovered that people with higher levels of lithium in their drinking water were less likely to be diagnosed with dementia compared to those whose tap water naturally contained lower lithium levels. Another large study published in 2022 from the United Kingdom showed that people prescribed lithium were about half, who have the diagnosis of Alzheimer’s in a control group, suggesting a protective effect of the drug.
But the use of lithium in psychiatry ensured that the type of cast became therapeutic, Yankner said. Nobody realized that it could be important for the normal physiology of the body.
That happened partly because the quantities of lithium that usually circulate in the body are so small that they could not be quantified until recently. Yankner and his team had to adjust new technology to measure it.
In the first phase of the research, the scientists tested the brain tissue and the blood of older patients collected by the Brain Bank at Rush University on track levels of 27 metals. Some patients had no history of memory problems, while others deteriorate early memory and had pronounced Alzheimer’s. Although there was no change in the levels of most metals they measured, Lithium was an exception. Lithium levels were consistently lower in patients with mild cognitive impairment or the Alzheimer’s compared to those with normal brain function. The brains of patients’ disease Alzheimer also showed increased levels of zinc and reduced copper levels, something scientists had previously observed.
Consistent finding lower lithium levels in the brain of people with memory loss came down to a smoking gun, Yankner said.
“First, to be honest, we were skeptical about the result because it was not expected,” said Yankner.
But it stopped, even when they checked monsters of other brain banks in Massachusetts General Hospital, Duke and Washington Universities.
“We wanted to know if this fall in the lithium was biologically useful, so we came up with an experimental protocol where we could selectively get lithium from the diet of mice and see what happens,” said Yankner.
When they fed the mice a diet with little lithium and simply drop their natural levels by 50%, their brains quickly developed characteristics of Alzheimer’s.
“The neurons started to degenerate. The immune cells in the brain became wild in terms of increased inflammation and poorer maintenance function of the neurons around them, and it looked more like an advanced Alzheimer patient,” Yankner said.
The team also found the gene expression profiles of Lithium-deficient mice and people who had Alzheimer’s disease was very similar.
The researchers then started to see how this fall in the lithium could occur. Yankner said in the earliest phases that there is a decrease in the absorption of lithium in the brain from the blood. They do not yet know exactly how or why it happens, but it probably comes from different things, including reduced diet intake, as well as genetic and environmental factors.
The most important source of lithium for most people is their diet. Some foods with the most lithium are leaf -green vegetables, nuts, legumes and some herbs such as turmeric and cumin. Some mineral waters are also rich sources.
In other words, Yankner said, many of the foods that have already proved to be healthy and reduce the risk of a person on dementia can be beneficial because of their lithium content.
“You know, people often find that things can have an effect, and you think you know exactly why, but then it turns out to be completely wrong about why,” he said.
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