Key Alzheimer’s Proteins Attack Different Brain Regions, Study Shows Need for Combined Treatment

Scientists have discovered that the two proteins linked to Alzheimer’s disease target different brain regions, suggesting current single-target treatments may be insufficient to combat the disease effectively. The research, published in Molecular Psychiatry, reveals how tau and beta–amyloid proteins work together to disrupt brain circuits controlling memory and emotions.

Using a novel mouse model that mimics both hallmarks of Alzheimer’s disease, researchers at the Institut de Neurociències of the Universitat Autònoma de Barcelona found that tau protein accumulation in the hippocampus leads to memory problems, while beta-amyloid buildup in the amygdala causes emotional disturbances like anxiety and fear.

“Although both proteins accumulate in the brains of Alzheimer’s patients, most animal models used for studying the disease typically focus on only one of these factors,” explained Maria Dolores Capilla, the study’s lead author. “In our research, we generated a transgenic mouse model exhibiting both tau and beta-amyloid accumulation, allowing us to analyze their individual and combined effects.”

The findings challenge current treatment approaches that typically target just one of these toxic proteins. “Existing therapies have not achieved clear clinical benefits. Our study suggests that a therapeutic approach addressing multiple disease mechanisms—such as phosphorylated tau and beta-amyloid—could be more effective,” said Carles Saura of the UAB Department of Biochemistry and Molecular Biology.

The research team discovered that when both proteins are present, they work together to intensify brain inflammation and cellular dysfunction, creating a more severe impact than either protein alone. This synergistic effect helps explain why previous treatments targeting only one protein may have shown limited success in clinical trials.

The study also revealed that female mice showed more severe symptoms in specific brain regions, mirroring clinical observations that women often experience faster cognitive decline in Alzheimer’s disease. This sex-specific vulnerability remains poorly understood and warrants further investigation.

Beyond identifying how these proteins affect different brain circuits, the research uncovered changes in multiple genes associated with inflammation and synaptic function—the connections between brain cells. These genetic changes occurred in brain regions crucial for memory and emotional processing, providing new potential targets for therapeutic intervention.

The research represents a significant shift in understanding how Alzheimer’s disease develops and progresses. While further studies are needed to confirm these findings in humans, the results suggest that future treatments may need to simultaneously target multiple disease mechanisms to be effective.

This comprehensive approach to understanding Alzheimer’s disease could help explain why current treatments have shown limited success and points toward new directions for developing more effective therapies that address multiple aspects of the disease simultaneously.