A groundbreaking study from the Wu Tsai Neurosciences Institute at Stanford University suggests that Alzheimer’s disease may erase memories by activating a molecular switch that prompts neurons to eliminate their own connections. Published on January 26, 2026, the research identifies how both amyloid beta and inflammation converge on a specific receptor, potentially leading to synapse loss. This discovery offers a new avenue for treating Alzheimer’s beyond existing therapies that primarily target amyloid beta.
The study was led by Carla Shatz, a professor at Stanford, alongside first author Barbara Brott, a research scientist in Shatz’s lab. Their findings, published in the Proceedings of the National Academy of Sciences, highlight a significant connection between two prominent theories regarding the onset of Alzheimer’s: the role of amyloid beta and chronic inflammation.
Understanding the Mechanism of Memory Loss
Alzheimer’s disease is notorious for its progressive destruction of brain cells and the neural connections vital for memory. The research indicates that amyloid beta, a protein fragment known to accumulate in the brains of Alzheimer’s patients, activates a receptor called LilrB2. This receptor signals neurons to prune synapses, the contact points that enable communication between brain cells. Previous studies by Shatz had already established the role of LilrB2 in synaptic pruning during brain development and learning.
The new research builds upon this foundation by exploring the relationship between amyloid beta and inflammation, which is recognized as a significant risk factor for Alzheimer’s. Shatz’s team investigated whether inflammatory molecules could also bind to LilrB2 and trigger synapse loss in a similar manner.
Identifying the Role of Inflammation
Through their experimentation, the researchers focused on the complement cascade, an immune process that helps eliminate pathogens and damaged cells. They discovered that the protein fragment C4d binds strongly to LilrB2, raising concerns that it may contribute significantly to synapse loss. Subsequent tests involving live mice demonstrated that injecting C4d into their brains resulted in the stripping away of synapses from neurons.
This finding challenges the prevailing assumption that glial cells, the brain’s immune cells, are solely responsible for synapse removal in Alzheimer’s. According to Shatz, “Neurons aren’t innocent bystanders; they are active participants,” indicating that neurons play a more direct role in the disease’s progression than previously thought.
Implications for Future Treatments
The implications of this research are profound for the future of Alzheimer’s treatment. Current FDA-approved therapies primarily aim to dismantle amyloid plaques in the brain, but Shatz notes that these drugs have limited effectiveness and considerable side effects, including headaches and brain bleeding.
“Even if they worked well,” she noted, “you’re only going to solve part of the problem.” Targeting receptors like LilrB2, which directly influence synapse removal, may provide a more effective strategy for preserving memory and mitigating the impact of Alzheimer’s.
The study involved a collaborative effort among researchers from various departments at Stanford University and other institutions, including the California Institute of Technology. Funding was provided by the National Institutes of Health and several foundations focused on neurodegenerative diseases.
As scientists continue to unravel the complexities of Alzheimer’s, this research emphasizes the need for a broader approach to understanding how memory loss occurs. By exploring alternative pathways and mechanisms, researchers hope to develop more effective treatments that cater to the multifaceted nature of this debilitating disease.
