Alzheimer’s disease is a neurodegenerative condition which leads to the progressive loss of memory, cognitive functions and autonomy. It is characterized by piles of beta-amyloid protein, neurofibrillar tangles of the tau protein and the loss of a protective protein called Rest-but these never explain the complete history of the disease. On the one hand because some people with such anomalies have no cognitive decline and on the other hand, recently developed treatment targeting the beta-amyloid protein have very modest efficiency. But a recent discovery may well have found a key element to better understand this disease.
Lithium deficiency, witness to Alzheimer’s advance
The study conducted by Professor Bruce Yankner at the Harvard Medical School analyzed the brain and blood of people at different stages of cognitive health by associating with the Rush Memory and Agging Project in Chicago, which has a bank of post-mortem cerebral tissue given by thousands of participants in the study covering the whole spectrum of health and diseases cognitive. The team measured the levels of traces of around 30 different metals in the brain and blood of cognitive health, people at an early stage of dementia called light cognitive disability and people with Alzheimer’s disease at an advanced stage. Result: lithium is the only metal whose rate drops early in those with light cognitive disorders or Alzheimer’s. An observation reproduced by the team with samples obtained from several brain banks in the United States.
Yankner and his colleagues went further. They have demonstrated in mice that lithium deficiency is not only linked to Alzheimer’s disease: it contributes to its development. Indeed, on a murin model, a lithium deficiency – caused by a limited diet – accelerates the signs of the disease: more abundant amyloid deposits, accumulation of tau, activation of inflammatory cells, loss of neural connections and decline of memory. Researchers have also shown that these deficits are linked to Lithium fixing on amyloid platesreducing its availability in the brain.
Supplementation made it possible to reverse the cognitive decline
But by testing thelithium orotatecapable of avoiding this capture, they managed to Restore memory, prevent brain damage and reverse pathological markerseven in mice at an advanced stage. In particular, maintaining a stable lithium rate at the start of life has prevented the appearance of Alzheimer’s disease, a discovery confirming that lithium feeds the pathological process.
“”What impresses me most with lithium is its general effect on the different manifestations of Alzheimer’s disease. I have never seen anything comparable since I have been working on this disease “said Prof. Yankner.
A well -known mineral, but here in tiny doses
Lithium has already been used for decades to treat bipolar disorders or major depressions, but in high doses that can be toxic, especially in the elderly. The use of lithium orotate in doses a thousand times lower that psychiatric treatments, the equivalent of the natural rate present in a healthy brain, would avoid these side effects. The mice treated for almost all their adult life with this tiny dose showed No signs of toxicity. If this discovery is confirmed in humans, it would make it possible to better identify people at risk and have preventive or even potentially curative treatment. As Bruce Yankner points out: “The idea that a lithium deficiency can be a cause of Alzheimer’s disease is new and suggests a different therapeutic approach “.
Despite his enthusiasm and these spectacular results in animals, the scientist remains cautious: “You have to be careful when extrapolated from Murine models, and you never know as long as you have not tried in a controlled clinical trial “. He also insists that: no question of taking lithium without medical supervision. This compound can be dangerous in the elderly, increase the risk of dehydration or damage kidneys in particular in associations with current drugs.
When will clinical trials in humans?
The goal is now launch clinical trials To confirm these effects in humans and, possibly, define a lithium threshold to maintain to prevent the disease. Nevertheless, this study once again pleads for an effect of lithium on the risk of dementia. In 2017, a Danish study revealed that people whose drinking water contained high rates of lithium had less risk of dementia than those whose water had lower lithium levels. Another study conducted in the United Kingdom had also shown that they had prescribed lithium was half less likely to be diagnosed with Alzheimer’s disease …
“”My hope is that lithium does something more fundamental than anti-amyloid or anti-slurry therapies, not only by attenuating but by reversing cognitive decline and improving the lives of patients “ concludes Prof. Yankner. Hopefully clinical trials can be quickly implemented in humans.