New Research Targets the Brain’s Own Amyloid-Clearing Enzyme
For years, the Alzheimer's research world has been laser-focused on one goal: clearing amyloid beta, the sticky protein that clumps into plaques and slowly disrupts brain function. Scientists have tried to remove these plaques directly, often with complex and costly antibody therapies.
Now, a new study1 has uncovered something that could change the equation entirely. Their findings, published in the Journal of Alzheimer's Disease, point to two specific brain receptors that appear to regulate the brain’s natural amyloid-clearing system.
And because these receptors belong to a family that’s already widely targeted in medicine, the discovery could eventually open the door to safer, more affordable treatments.
How the brain already clears amyloid (and why it stops working)
Your brain isn't defenseless against amyloid buildup. It produces an enzyme called neprilysin that naturally breaks down amyloid beta before it can accumulate. The problem is that neprilysin levels decline with age and drop further as Alzheimer's progresses, essentially leaving the brain's cleanup crew understaffed right when it's needed most.
The researchers set out to understand exactly what controls neprilysin production in the first place. What they found were two receptors called SST1 and SST4, both belonging to a family of proteins called somatostatin receptors, that work together to regulate neprilysin levels in the hippocampus, the brain region most critical for memory.
What the researchers did
The team used a combination of genetically modified mice and lab-grown cells to map out this receptor system. Here's what the experiments revealed:
- When both SST1 and SST4 receptors were removed, neprilysin levels dropped significantly in a key region of the hippocampus
- Mice without these receptors showed increased amyloid beta buildup and measurable memory problems
- When researchers treated mice that already had Alzheimer's-like brain changes with a compound designed to activate SST1 and SST4, neprilysin levels went back up, amyloid beta decreased, and behavior improved
- Crucially, the treatment did not produce serious side effects
How this approach is different
Today’s most advanced Alzheimer’s drugs largely focus on clearing amyloid after it has accumulated. This new strategy is different. It aims to strengthen the brain’s own amyloid-clearing system.
Instead of introducing external antibodies, researchers are exploring whether small molecules could stimulate SST1 and SST4, boosting neprilysin and reducing plaque buildup from within.
Of course, this research was conducted in mice, not humans. We are still far from a pharmacy-ready pill. But identifying specific receptor targets that regulate neprilysin is a meaningful step forward.
The takeaway
This research is still in early stages. Mouse models are a necessary first step, but human trials are a ways off.
But there are a few reasons this study feels hopeful.
First, it provides a more precise understanding of how amyloid beta is regulated in the brain. Second, it highlights drug targets that are already well understood in pharmacology, which could accelerate future development. And third, it shifts the narrative from simply removing plaques to restoring balance in the brain’s own protective systems.
For now, the most evidence-based strategies for reducing dementia risk remain lifestyle-focused: regular physical activity, metabolic health, quality sleep, social engagement, and cognitive stimulation all play powerful roles in brain health.