Many recent animal studies have suggested lithium may be beneficial in treating Alzheimer’s disease. A new study in rats adds to this data, showing that even at its later stages, a microdose of the drug can stop the progression of this neurodegenerative disease.
Medical News Today reported on a study in 2017 that proposed the lithium mood stabilizer could help stave off dementia.
The study found that people exposed to drinking water with higher lithium concentrations were 17 per cent less likely to develop dementia than those whose water barely contained lithium.
Other epidemiological, preclinical, and clinical studies have since suggested that a lithium microdose can reduce the risk of Alzheimer’s by influencing key pathological mechanisms in the neurodegenerative condition at play.
The journal Translational Psychiatry published one such study. The study found that lithium concentrations hundreds of times lower than what doctors usually prescribe in rat models for psychiatric conditions such as bipolar disorder may help improve early signs of Alzheimer’s disease.
Dr. Claudio Cuello— the senior author of that study at the Department of Pharmacology and Therapeutics at McGill University, Quebec, Canada.
Now Dr. Cuello and his research team have undertaken to investigate whether or not lithium microdoses would have the same beneficial effects at later stages of the condition.
The authors published their new findings in the Journal of Alzheimer’s Disease.
Testing the old microdose in new rats
“An early stage of amyloid pathology in Alzheimer’s transgenic rat, microdoses of lithium at concentrations hundreds of times lower than those applied in the clinic for mood disorders were administered,” explains Dr. Cuello, speaking of his previous research.
The researchers named the prepared lithium microdose NP03. They applied it to a transgenic Alzheimer’s model in their previous study, in which rats expressed human proteins that triggered characteristics of Alzheimer’s disease, such as toxic accumulation of amyloid plaques in the brain and cognitive issues.
“These results were remarkably positive, and […] they stimulated us to continue working with this approach on a more advanced pathology,” Dr. Cuello said.
So, the researchers in the new study administered the same dose to transgenic rats at the equivalent of late preclinical stages of human Alzheimer’s disease. The beta-amyloid had already accumulated at this post-plaque stage to such an extent that it had begun to affect the cognition.
The rats took the lithium for 12 weeks, and the researchers used the novel object recognition test to assess their remote working memory. Dr. Cuello and colleagues also looked at neuroinflammation markers in the brains of the rodents, oxidative stress levels and beta-amyloid levels.
Lithium effective after toxic plaque buildup
According to the authors of the study, “NP03 rescues functional deficits in object recognition” tests, “reduces levels of cortical soluble and insoluble” beta-amyloid, and reduces the number of plaques in the hippocampus of the brain.
“The NP03 also reduces markers of neuroinflammation and cellular oxidative stress,” they write. Together, these results indicate that, after[ beta-amyloid] plaques appear, microdose lithium NP03 is effective at later stages of amyloid pathology.
“While it is unlikely that any medication will revert irreversible brain damage at Alzheimer’s clinical stages, it is highly likely that treatment with encapsulated lithium microdoses should have tangible beneficial effects at early, preclinical stages of the disease.”
– Dr. Claudio Cuello
He is hopeful that the findings of the team will soon be translated into clinical trials, either testing NP03 with other drug candidates or testing it in high-risk populations of Alzheimer’s or adults already having preclinical Alzheimer’s.
“From a practical point of view, our findings show that lithium microdoses should find immediate therapeutic applications in formulations such as the one we used, which facilitates the passage into the brain through the blood-brain barrier while minimizing lithium levels in the blood, sparing people from adverse effects,” says Dr. Cuello.
