Clumps or plaques of the protein beta-amyloid in the brain are a hallmark of a type of dementia called Alzheimer’s disease. For example, two anti-amyloid medications, lecanemab and donanemab, are FDA-approved to help decrease the number of plaques in people with early Alzheimer’s. The study was recently published in the journal Science Signaling.
Neprilysin is an endopeptidase, the scientific term for an enzyme that divides peptide bonds. Past studies have also examined the potential role neprilysin may play in Alzheimer’s disease as it has shown to be effective in degrading beta-amyloid in the brain. A study published in December 2023 reported that using a neprilysin inhibitor led to increased beta-amyloid.
Research published in December 2022 found injecting a form of neprilysin that can penetrate the blood-brain barrier showed the potential to reduce beta-amyloid plaques in the brain. To conduct this study, scientists first found when they applied dopamine to brain cells cultured in a dish, neprilysin levels increased and levels of free-floating beta-amyloid decreased.
Next, using a mouse model, researchers used the Designer Receptors Exclusively Activated by Designer Drugs (DREADD) system to insert minute designer receptors into the dopamine-producing neurons in the ventral tegmental area of the brain, which is known to stimulate dopamine neurons.
Scientists also fed the mice a matching designer drug. Researchers then applied this method to a special mouse model of Alzheimer’s disease where the mice develop beta-amyloid plaques.
For the final step of the study, researchers applied their methodology to L-DOPA treatment, a dopamine precursor molecule used to treat Parkinson’s disease. But L-DOPA treatment is known to have serious side effects in patients with Parkinson’s disease. Therefore, the next step is to investigate how dopamine regulates neprilysin in the brain, which should yield a new preventive approach that can be initiated at the preclinical stage of Alzheimer’s disease. Parulekar said it is important for researchers to continue to find new ways of combating Alzheimer’s disease because it is a devastating disease that affects millions of people worldwide.
Alzheimer’s remains a devastating illness for patients and their loved ones. The anti-amyloid treatment approaches have failed to solve the problem, though perhaps this idea will lead to new ways of combating Alzheimer’s disease. And identify the mechanisms by which dopamine regulates neprilysin levels in the brain. This will help to develop new and more targeted treatments for Alzheimer’s disease. Researchers also said that we need to know how dopamine causes neprilysin levels to increase and why does that then decrease amyloid plaque buildup.
