A brain deficiency in lithium at the origins of the disease?

What at the very beginning, triggers Alzheimer’s disease? A team of researchers from the Harvard Medical School may have found the answer to this question that has tapped neuroscientists from around the world for decades. Lithium. A brain deficiency could be the key.

Nearly 400 million people suffer from Alzheimer’s disease, the first neurodegenerative disease worldwide, representing 60 to 80 % of dementia. This implies a set of brain abnormalities: an accumulation of beta-amyloid protein, neurofibrillar tanglings of the Tau protein and, less known, the decline of a protective protein called Rest. But the beginning of the story is still not understood.

Previous studies had revealed anomal metal concentrations in people with Alzheimer’s disease. Based on this observation, the researchers compared the concentrations of 27 metals in the brains of the elderly without cognitive disorder to that of people with disorders. The laboratory joined forces with Rush Memory and Aging Project From Chicago, which has a bank of post-mortem cerebral tissue, representing the whole spectrum of cognitive health of people in full mental shape with those with advanced Alzheimer.

First discovery: “This is the first time that we have proven that lithium has naturally existed at a biologically useful level, without being administered in the form of a medication”, explains Bruce Yankner, professor of genetics and neurology, in a press release from Harvard University.

Second discovery: lithium presented significantly low brain concentrations in people diagnosed with Alzheimer’s but also in those with light cognitive disorders. In Alzheimer’s patients, the amount of lithium was less in areas close to amyloid deposits. Same thing in genetically modified mice to develop Alzheimer’s disease. “This discovery confirmed that the amyloid captures lithium of the surrounding tissues and the sequestration”, We read in an article in the journal Naturewhere this study was published on Wednesday August 6. Thus trapped, lithium is no longer absorbed by the brain and could no longer fulfill its protective functions.

Healthy mice and model mice of Alzheimer’s disease then followed a diet low in lithium. In the former, lithium levels dropped to rates similar to those observed in patients with Alzheimer’s. This has accelerated aging, causing inflammation in the brain, loss of connections between neurons, and a cognitive decline.

In models, this drop in lithium has considerably accelerated the formation of amyloid plaques and structures similar to neurofibrillalar tangles. It has also activated immune cells in the brain (microglies), reducing their ability to eliminate the amyloid and accelerate memory loss.

Why does lithium deficiency cause these effects? Researchers are unable to answer this question for the time being. But they hypothesized that another type of lithium may not be trapped by amyloid plates. They then tried their luck on the mice with different lithium salts. One of them, the lithium orotate, made it possible to reverse the damage linked to Alzheimer’s disease; The accumulation of beta-amyloids and tau protein, the appearance of cognitive disorders and signs of inflammation. Even in the elderly mice at an advanced stage of the disease. It also allowed the immune cells of the brain, whose capacities decrease with age, to regain their ability to degrade the amyloid-β.

Tested in non -genetically modified mice, lithium orotate made it possible to prevent the decline in learning and memory capacities, a decline linked to a loss of neural architecture, normal in the elderly.

“What impresses me the most is the generalized effect of lithium on the various manifestations of Alzheimer’s disease. I have never observed anything like this since I have been working on this disease ”, continues Bruce Yankner.

These results must still be confirmed in humans but they suggest that the measurement of lithium levels could contribute to the early detection of Alzheimer’s disease. As for lithium orotate, it could be used for therapies or preventive.

Lithium is used today as treatment of bipolar disorders and major depressive disorders. Administered at high doses, it is potentially toxic, especially for kidneys and thyroid, in vulnerable people like the elderly. But the doses necessary to restore the normal level of lithium in the brain are infinitely smaller. And the mice treated with lithium for these experiences have had no sign of toxicity.

“Very powerful effects have been observed with an extremely low dose”, said Yankner before adding: “I hope that lithium will be able to do something more fundamental than anti-amyloid or anti-mud therapies-not only reduce cognitive decline, but also reverse it, and thus improve the lives of patients.” Treatments currently available have only very modest effects on the progression of the disease with heavy side effects.