Drug Already Approved For Parkinson's Could Help Clear Alzheimer's Brains
Parkinson's and Alzheimer's disease are both the result of a steady loss of neurons, yet each operates in different areas of the brain under very different conditions.
A new study suggests that a medication already approved for use in people with Parkinson's could serve another purpose, allowing it to enhance treatments that could help clear toxic clumps thought to be responsible for the most common form of dementia.
On entering the brain, the drug – called levodopa (or L-DOPA) – turns into the hormone dopamine; a neurotransmitter closely linked to feelings of pleasure and motivation and known to be lacking in brains affected by Parkinson's.
This new study, led by researchers from the RIKEN Center for Brain Science in Japan, found that the application of dopamine to the brains of mice with an Alzheimer's-like disease was linked to improvements in physical symptoms and memory.
The target for the dopamine-boosting drug is the enzyme neprilysin. Previous studies have shown this enzyme can break down clumps of the beta-amyloid protein that clog up Alzheimer's brains and destroy neurons along the way.
Unfortunately neprilysin can't enter the brain from the bloodstream to clear the toxic mess, so the scientists needed a way to smuggle the enzyme across the body's borders.
Through a comprehensive series of lab tests, the team discovered that applying dopamine to cortical, hippocampal, and basal ganglia neurons led to a boost in neprilysin levels and a breakdown in beta-amyloid plaques. Further tests in living mice had the same effect: dopamine increased neprilysin production, and cut down on the brain damage linked to Alzheimer's.
As a precursor that converts to dopamine inside the brain, levodopa was the final link in the chain of experiments. The team also observed drops in dopamine and neprilysin in older mice, perhaps another important clue to the development of Alzheimer's.
"Aged mice had less dopamine and neprilysin in the anterior cortex, a decrease that was accentuated in Alzheimer's disease model mice," write the researchers in their published paper.
"Treating Alzheimer's disease model mice with levodopa reduced beta-amyloid deposition and improved cognitive function."
This is all very promising, but plenty of questions remain. The researchers aren't sure why dopamine raises neprilysin levels, for example.
While levodopa is universally approved as a treatment for Parkinson's, it's not without its own adverse effects, especially when used long term. Clinical trials are going to be needed to see if these same results can be replicated in humans, and to make sure the treatment isn't doing more harm than good.
"L-DOPA treatment is known to have serious side effects in patients with Parkinson's disease," says RIKEN neuroscientist Watamura Naoto.
"Therefore, our 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."
The research has been published in Science Signaling.