On Apr. 7, 2025, in a landmark study, researchers at University of Nebraska Medical Center (UNMC) announced they have developed a novel mouse model of Alzheimer’s disease that, for the first time, enables the study of how the human immune system interacts with Alzheimer’s pathology.

These models facilitate translational research, bridging the gap between preclinical research and human clinical trials, particularly in developing next-generation neuroprotective therapies.

For example, Dr. Lee Mosley, PhD, one of the team leaders, said past vaccine studies targeting amyloid plaques were adequate in mice but caused severe immune reactions, leading to brain swelling, in human trials. “These failures reflect a deeper issue,” he said. “The models lack the complexity of the human immune and genetic landscape.”

The team used CRISPR-Cas9 knock-in technology to knock in early-onset familial Alzheimer‘s-associated genes while preserving replicate human gene expression patterns, thus more accurately reflecting the true disease.

The models, developed at UNMC, were described in two papers, one in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, and another in Neuroimmune Pharmacology and Therapeutics.