Lithium deficiency may be the hidden spark behind Alzheimer’s

• The study shows for the first time that lithium plays a fundamental role in the normal brain function and can give resistance to encephal aging and Alzheimer’s disease.
• Scientists have discovered that lithium is exhausted in the brain by linking to toxic amyloid paintings – which reveals a new method that may start Alzheimer’s.
• A new category of lithium -based compounds avoids plaque connecting and reflects Alzheimer’s and the sheikh of the brain in mice, without toxicity.

What is the oldest spark that ignites Alzheimer’s disease in Alzheimer’s memory? Why do not some people with Alzheimer’s in the brain continue to develop dementia? These questions have decades -sex neuroscientists.

Now, a team of researchers at the Harvard University College of Medicine has found an answer: lithium deficiency in the brain.

Work, published on August 6 in natureIt appears for the first time that lithium occurs naturally in the brain, protects it from nervous degeneration, and maintains the natural function of all main types of brain cells. The results – 10 years are based on making – are based on a series of experiments in mice and on human brain tissue analyzes and blood samples from individuals at various stages of cognitive health.

Scientists have found that lithium loss in the human brain is one of the first changes that lead to Alzheimer’s disease, while in mice, the similar lithium exhausted the accelerated brain diseases and low memory. The team also found that low lithium levels stem from the bonding with amyloid paintings and weak absorption in the brain. In a final group of experiments, the team found that the new lithium compound that avoids captured by the amyloid plaques that were restored in the mice.

The results unite decades -long notes in patients, providing a new theory of the disease and a new strategy for early diagnosis, prevention and treatment.

This affects an estimated 400 million people worldwide, and Alzheimer’s disease includes a group of brain deformities – such as beta -amyloid protein blocks, fibroid tangles of the Tau protein, and a loss of protective protein called comfort – but this did not explain the full story of the disease. For example, some people who suffer from such deformities do not show any signs of cognitive decline. Recently developed treatments that target the amyloid beta usually do not reflect memory loss and reduce the decline rate.

It is also clear that genetic and environmental factors affect the risk of Alzheimer’s disease, but scientists have not discovered the reason for the development of some people who have the same risk factors while others do not.

The authors of the study said that lithium may be a missing link.

“The idea that lithium deficiency can be a new cause of Alzheimer’s disease and suggests following a different treatment approach,” said Bruce Yannerner, authors of Genetics and Neuroscience at the Blavatnik Institute in HMS, who was the first to show that the amyloid beta is toxic.

He said that the study raises hopes that researchers can use lithium one day to treat the whole disease instead of focusing on one side such as the amyloid or Tao beta.

One of the main discoveries in the study is that with the start of an amyloid experimental in the formation of deposits in the early stages of dementia in both humans and mouse, it is associated with lithium, which reduces the function of lithium in the brain. Low lithium levels affect all types of main brain cells, and in mice, they lead to changes to customizer customization, including memory loss.

The authors have identified a category of lithium compounds that can escape capture by the amyloid beta. Treatment of mice with the most powerful amyloid compound, called Orotate lithium, unlike Alzheimer’s disease, prevent brain cell damage, and recovery memory.

Although the results need emphasis on humans through clinical trials, they indicate that measuring lithium levels can help in the screen for early Alzheimer’s disease. Moreover, the results indicate the importance of testing lithium compounds that conflict with amyloid for treatment or prevention.

Other lithium compounds are already used to treat bipolar disorder and severe depression, but they are given with much higher concentrations that can be toxic, especially for the elderly. The Yankner team found that the Orotate lithium is effective at the thousand dose-enough to imitate the normal level of lehium in the brain. The mice that were treated for the lives of the entire adults have not shown any evidence of toxicity.

“You have to be careful about extrapolation of mouse models, and you never know even try it in a censorship clinical experience,” said Yannner. “But the results so far are very encouraging.”

Lithium exhaust is an early sign of Alzheimer’s disease

Yankner became interested in lithium while using nerve proteins. However, knowing whether legeium is present in the human brain and whether its levels change with the development of nervous degeneration and progress, however, it requires reaching the brain tissue, which is generally not accessible in living people.

So, the laboratory has a partnership with the Rush Memory and AGing project in Chicago, which contains a bank post -death tissue that thousands of participants in the study via the full spectrum of health and cognitive disease donated.

Yankanner said that the presence of this range was very important because trying to study the brain in the late stages of Alzheimer’s disease is similar to looking at the battlefield after the war. There is a lot of harm and it is difficult to know how everything started. But in the early stages, “before the brain is damaged badly, you can get important evidence.”

Under the first author Levio Aaron, a senior researcher at the Yankanner Laboratory, the team used an advanced type of comprehensive spectral analysis to measure the trace levels of about 30 different minerals in the brain and the blood of healthy people perceived, and those in an early stage of dementia called moderate cognitive weakness, and those who suffer from advanced Alzheimer.

Lithium was the only metal that had significantly different levels across groups and changed in the early stages of memory loss. Its levels were high in healthy donors, but they have been dramatically reduced in those with moderate weakness or complete Alzheimer’s disease.

The team repeated its results in the samples obtained from multiple brain banks in the country.

The observation is in line with previous population studies that show that lithium levels are high in the environment, including in drinking water, followed by low dementia.

However, the new study by monitoring lithium directly in the brains of people who did not receive lithium as a treatment, has set a scope that constitutes normal levels, and explains that lithium plays a fundamental role in brain physiology.

“It turns out that lithium is like the other nutrients that we get from the environment, such as iron and vitamin C,” said Yannner. “It is the first time that anyone has appeared that lithium is at a normal biological level without giving it as a medicine.”

Then Yankanner and his colleagues took a step forward. They have shown in the mice that the exhaustion of lithium is not only associated with Alzheimer’s disease – it helps to push it.

Lithium loss leads to the scope of changes related to Alzheimer’s

The researchers found that feeding healthy mice followed a restricted diet in lithium brought lithium levels to the brain to a level similar to those in patients with Alzheimer’s disease. This appears to speed up the aging process, which led to brain inflammation, loss of interlocking bonds between neurons, and cognitive decrease.

In Alzheimer’s mouse models, the lifesty lithium has accelerated significantly to form beta -like amyloid and structures that resemble nervous tangles. Lithium exhaustion also activated inflammatory cells in the brain called MicroGlia, which weakens its ability to deteriorate amyloid; It causes the loss of nerve clamps, axes and the port of neurons. The accelerated cognitive decrease and memory loss – all the distinctive features of Alzheimer’s disease.

Mouse experiments also revealed that lithium changed the activity of genes known to increase or decrease the risk of Alzheimer’s, including the most famous, Patriarchal.

The regeneration of lithium by giving lithium mice in its water contrary to the damage associated with the disease and the recovery memory function, even in the ancient mice with advanced disease. It is worth noting that maintaining stable levels of lithium in early life prevent the appearance of Alzheimer’s disease – a discovery that lithium feeds the disease process.

“What a more admiration about the lithium is the widespread influence that I have on the various aspects of Alzheimer’s. I saw nothing just like him throughout the years of working on this disease,” said Yannner.

A promising way to treat Alzheimer’s

Some clinical trials of lithium of Alzheimer’s disease showed some effectiveness, but the lithium compounds they used – such as the clinical standard, lithium carbonate – can be toxic to aging in high doses usually used in the clinic.

The new research explains the reason: The amyloid beta was tool for these other lithium compounds before you could work. Yankner and his Lithium colleagues are found by developing an examination platform looking for a library of vehicles for those who may exceed the amyloid beta. Other researchers can now use the arterial system to search for additional Lithium compounds that challenge the amyloid that may be more effective.

“One of the most allied results for us was that there are profound effects on this wonderful low dose.”

If it is repeated in more studies, the researchers say that lithium examination through routine blood tests may one day provide a way to identify individuals at risk of Alzheimer’s who will benefit from treatment to prevent or delay the appearance of the disease.

Yankanner said that studying lithium levels in people who resist Alzheimer’s disease because age may help scientists create a targeted level that can help patients maintain the appearance of the disease.

Since lithium has not yet been proven that it is safe or effective in protecting against nervous degeneration in humans, Yanker emphasizes that people should not take lithium compounds alone. But he expressed cautious optimism that Orotate lithium or a similar compound will move forward in clinical trials in the near future and can eventually change the story of Alzheimer’s treatment.

“I hope that lithium will do something more essential than anti -amyid or Tau anti -aid treatments, not just reduce but the opposite of cognitive decline and improving patients’ lives,” he said.

Written, financing, disclosure

Additional authors are Chen Kai Nagian, Chenshi Choi, Jaejun Choi, Mariana Liang, Derek M. Drake, Sarah E. Hambova, Ella Lassi, Pearl Roche, Monlan Yuan, and SABA HMS music; Eunjung A. Lee from Boston Children’s Hospital; And David a. Bennett from Alzheimer’s disease at the Rush University Medical Center in Chicago.

Yankner is the co -manager of the Paul F. Glenn Biology for Aging Research in HMS.

This work has been supported by the National Institutes of Health (Grants R01ag046174, R01ag069042, K01ag051791, DP2AG072437, P30Ag10161, P3ag72975, R01ag15819, R01ag17917, U01ag46152, and U01ag61356), Ludwig Family Foundation, and Glenn Medical Research and the Age of Mind Foundation.