Dopamine may treat Alzheimer Disease (AD)
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A stunning discovery, which flies in the face of everything that medicine claims to know about dopamine. Official medical dogma views dopamine as largely a nuisance, and even danger to human health. High dopamine levels are thought to be responsible for serious conditions such as schizophrenia, as well as virtually all types of addiction (substance, gambling, sexual, etc). As such, there is a large number of dopamine antagonist drugs and a much smaller set of dopamine agonists. Now, dopamine is known to have a pro-cognitive effect and this has resulted in the development of amphetamine-based chemicals such as Adderall, Ritalin, Provigil, etc that are now abused on a mass scale by virtually every white-collar profession in a quest to enhance cognitive function and outcompete peers intellectually in a corporate setting. Unbeknownst to most, serotonin has also been (very, very quietly) suspected as a cause of AD and there have even been several clinical trials with suboptimal serotonin antagonists as treatment for AD. The study below demonstrates that dopamine has a plaque-dissolving effect and suggests that this is the main mechanism of action through which dopamine may treat AD. However, 99% of all AD trials based on drugs targeting the beta or tau amyloid plaques have been utter failures, which suggests that the plaque-busting effects of dopamine are not the real explanation. Also unbeknownst to most, dopamine (and dopamine agonists) are potent inhibitors of the enzyme tryptophan hydroxylase (TPH), which is the rate-limiting step for producing serotonin inside the body. If serotonin is indeed a major cause of AD, then the serotonin-reducing properties of dopamine (and dopamine agonists) are probably the true mechanism of action behind the beneficial effects seen in the study below.
https://doi.org/10.1126/scisignal.adk1822
Melting Away Alzheimer’s: How Dopamine Dissolves Harmful Brain Plaques
“…A new way to combat Alzheimer’s disease has been discovered by Takaomi Saido and his team at the RIKEN Center for Brain Science (CBS) in Japan. Using mice with the disease, the researchers found that treatment with dopamine could alleviate physical symptoms in the brain as well as improve memory. Published today (August 6) in the scientific journal Science Signaling, the study examines dopamine’s role in promoting the production of neprilysin, an enzyme that can break down the harmful plaques in the brain that are the hallmark of Alzheimer’s disease. If similar results are found in human clinical trials, it could lead to a fundamentally new way to treat the disease.”
“…Now the serious experiments began. Using a DREADD system, they inserted tiny designer receptors into the dopamine-producing neurons of the mouse ventral tegmental area. By adding a matching designer drug to the mice’s food, the researchers were able to continuously activate those neurons, and only those neurons, in the mouse brains. As in the dish, activation led to increased neprilysin and decreased levels of free-floating beta-amyloid, but only in the front part of the mouse brain. But could the treatment remove plaques? Yes. The researchers repeated the experiment using a special mouse model of Alzheimer’s disease in which the mice develop beta-amyloid plaques. Eight weeks of chronic treatment resulted in significantly fewer plaques in the prefrontal cortex of these mice.”
“…The DREADD system is an incredible system for precise manipulation of specific neurons. However, it is not very useful for human clinical settings. The final experiments tested the effects of L-DOPA treatment. L-DOPA is a dopamine precursor molecule often used to treat Parkinson’s disease because it can enter the brain from the blood, where it is then converted into dopamine. Treating the model mice with L-DOPA led to increased neprilysin and decreased beta-amyloid plaques in both frontal and posterior parts of the brain. Model mice treated with L-DOPA for 3 months also performed better on memory tests than untreated model mice. Tests showed that neprilysin levels naturally decreased with age in normal mice, particularly in the frontal part of the brain, perhaps making it a good biomarker for preclinical or at-risk Alzheimer’s disease diagnoses. How dopamine causes neprilysin levels to increase remains unknown, and is the next research topic for Saido’s group.”