Dopamine Shows Promise in Reducing Alzheimer’s Symptoms

Researchers from the RIKEN Center for Brain Science have recently revealed a new treatment that uses dopamine for Alzheimer’s disease. It can reduce physical symptoms and improve memory in a mouse model. 

This study was recently published in Science Signaling and explored dopamine’s role in promoting neprilysin production. It is an enzyme that breaks down Alzheimer’s disease plaques in the brain. If it shows similar results in human trials, it can help experts develop some new treatment methods that effectively treat this memory disease. 

Hardened amyloid plaques around neurons are early signs of Alzheimer’s disease. The process of formation of these amyloid plaques begins decades before a person with Alzheimer’s disease shows some behavioral symptoms like memory loss.  

In this study, researchers focused on the enzyme neprilysin. It has been shown to reduce beta-amyloid plaques and improve memory in mice through genetic manipulation. But to treat Alzheimer’s disease, neprilysin pills or injections are not feasible as it cannot enter the brain from the bloodstream. 

This study screened many molecules to determine which ones can naturally upregulate neprilysin in the brain. The team focused on hormones produced by the hypothalamus and they found that applying dopamine to brain cells cultured in a dish increased neprilysin levels and reduced free-floating beta-amyloid levels. 

Researchers used a DREADD system to insert tiny designer receptors into neurons that produce dopamine in the mouse ventral tegmental area. Then they added a matching drug to the mice’s food and could continuously activate these neurons. This treatment increased neprilysin and decreased beta-amyloid levels in the front part of the mouse brain. But it also successfully removed plaques. 

Researchers again conducted this experiment that involved a group of mice with Alzheimer’s disease. When they observed the results, they found that this chronic treatment for eight weeks significantly reduced beta-amyloid plaques in the prefrontal cortex. 

The DREADD system is a precise tool for manipulating specific neurons. But it may not be highly effective in human clinical settings. 

In the final experiments, researchers evaluated the impact of L-DOPA treatment- a dopamine precursor molecule that is commonly used to treat Parkinson’s disease, as it enters the brain and converts into dopamine. 

When researchers observed the results, they found that L-DOPA treatment increased the levels of neprilysin and reduced beta-amyloid plaques in both frontal and posterior brains. Three-month treatment improved memory performance as compared to untreated mice. 

These tests have revealed that neprilysin levels naturally decrease with age in normal mice, particularly in the frontal brain. It is a biomarker for preclinical or at-risk Alzheimer’s disease diagnoses. But the cause of dopamine-induced neprilysin increase is still unknown. 

Researchers of this study said that L-DOPA treatment can reduce harmful beta-amyloid plaques and enhance memory function in a mouse model of Alzheimer’s disease. But this treatment has serious side effects in Parkinson’s disease patients. They also said that there is a need for further research to understand more about how dopamine regulates neprilysin in the brain. This will help them develop new effective treatments for Alzheimer’s disease. 

Reference Link:  

The dopaminergic system promotes neprilysin-mediated degradation of β-amyloid in the brain, Science Signaling (2024).  

DOI: 10.1126/scisignal.adk1822,