Scientists Discover Brain 'Switches' That Clear Alzheimer's Plaques — Opening Door to Cheaper, Safer Treatment

Alzheimer's disease is the leading cause of dementia worldwide, marked by sticky clumps of amyloid beta (Aβ) forming plaques in the brain. While current antibody-based treatments can target these plaques, they cost tens of thousands of dollars per year and can cause significant side effects. Now, scientists at Karolinska Institutet in Sweden and the RIKEN Center for Brain Science in Japan have identified a potentially game-changing alternative. Their research, published in the Journal of Alzheimer's Disease, reveals that two somatostatin receptors — SST1 and SST4 — work together to control levels of neprilysin, an enzyme that naturally helps clear away amyloid beta in the hippocampus, the brain region essential for memory. Normally, neprilysin activity declines with aging and as Alzheimer's progresses. But the researchers found that when they stimulated both SST1 and SST4 receptors in mice with Alzheimer's-like brain changes, neprilysin levels increased, amyloid beta buildup was reduced, and the mice showed improved behavior and memory — without serious side effects. Conversely, when both receptors were genetically removed, neprilysin levels dropped, amyloid beta accumulated, and the mice developed memory problems. 'Our findings show that the brain's own defence against amyloid beta can be strengthened by stimulating these receptors,' says Per Nilsson, docent at Karolinska Institutet's Department of Neurobiology, Care Sciences and Society. The most exciting implication: unlike today's expensive antibody therapies, this approach could lead to small-molecule drugs that cross the blood-brain barrier — potentially treating Alzheimer's at a fraction of the current cost. 'If we can instead develop small molecules that pass the blood-brain barrier, our hope is that we will be able to treat the disease at a significantly lower cost and without serious side effects,' says Nilsson. With over 55 million people living with dementia globally — a number expected to reach 139 million by 2050 — a cheaper, safer treatment could be transformative for families and healthcare systems worldwide.