{"id":121159,"date":"2025-04-07T02:00:00","date_gmt":"2025-04-07T07:00:00","guid":{"rendered":"https:\/\/www.unmc.edu\/newsroom\/?p=121159"},"modified":"2025-04-07T07:37:15","modified_gmt":"2025-04-07T12:37:15","slug":"unmc-researchers-develop-new-tool-to-research-alzheimers-treatments","status":"publish","type":"post","link":"https:\/\/www.unmc.edu\/newsroom\/2025\/04\/07\/unmc-researchers-develop-new-tool-to-research-alzheimers-treatments\/","title":{"rendered":"New mouse models can bridge gap in Alzheimer\u2019s research"},"content":{"rendered":"
\n

In a landmark study, researchers at UNMC developed a novel mouse model of Alzheimer\u2019s disease that, for the first time, enables the study of how the human immune system interacts with Alzheimer\u2019s pathology.<\/p>\n\n\n\n

Pravin Yeapuri, PhD, R. Lee Mosley, PhD, and Howard Gendelman, MD, of the UNMC Department of Pharmacology and Experimental Neuroscience led the investigative team.<\/p>\n\n\n\n

The models, developed at UNMC, were described in two recently released papers, one in Alzheimer\u2019s & Dementia: The Journal of the Alzheimer\u2019s Association, and another in Neuroimmune Pharmacology and Therapeutics<\/a>, a journal created and developed by Dr. Gendelman at UNMC with the Society on NeuroImmune Pharmacology.<\/p>\n\n\n\n

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

\u201cPrior mouse models commonly used for disease prevention and therapeutic interventions to ameliorate Alzheimer\u2019s are significantly limited in their ability to reflect the natural disease course,\u201d Dr. Mosley said. \u201cWhile these models show cognitive improvement with experimental treatments, they have a poor track record of human clinical trial success.\u201d<\/p>\n\n\n\n

For example, Dr. Mosley said past vaccine studies targeting amyloid plaques were adequate in mice but caused severe immune reactions, leading to brain swelling, in human trials. \u201cThese failures reflect a deeper issue,\u201d he said. \u201cThe models lack the complexity of the human immune and genetic landscape.\u201d<\/p>\n\n\n\n

\u201cWhile CRISPR-engineered mouse models have helped us accurately knock in Alzheimer\u2019s-related genes, they miss key features like widespread neuronal loss and neuroinflammation,\u201d Dr. Gendelman said. \u201cOur new models go much further. They show robust neuronal degeneration and can be reconstituted by the human immune system. This opens the door to studying how human immune cells respond to human Alzheimer\u2019s-related proteins, something no previous model could do.\u201d<\/p>\n\n\n\n

Dr. Gendelman said this overcomes the major limitations of earlier models, which relied on non-physiological gene overexpression and lacked human immune components.<\/p>\n\n\n\n

The team used CRISPR-Cas9 knock-in technology to knock in early-onset familial Alzheimer\u2018s-associated genes while preserving replicate human gene expression patterns, thus more accurately reflecting the true disease.<\/p>\n\n\n\n

\u201cThese new models are critical to our recent work on T cell-based immunotherapies,\u201d Dr. Yeapuri said. \u201cThey let us test how the human immune system responds to Alzheimer\u2019s immunotherapies in a disease-relevant environment. That\u2019s a significant leap forward.<\/p>\n\n\n\n

\u201cThese models now allow us to simulate human clinical trials in mice equipped with a human immune system, enabling the study of regulatory T cells, tau pathology and neurodegeneration in a physiologically relevant context. They also support testing antibody-based therapies in a system that closely mirrors human biology.”<\/p>\n\n\n\n

Dr. Gendelman emphasized that the new platform sets the stage for future clinical trials, which his team has been working toward for decades. \u201cWith these tools in hand, we\u2019re closer than ever to developing therapies that work in people,\u201d he said. \u201cThe future of Alzheimer\u2019s treatment is finally within reach.\u201d<\/p>\nW IcDZHYXDW<\/a><\/div><\/div>","protected":false},"excerpt":{"rendered":"

UNMC researchers published a study on a new humanized mouse model expected to set the stage for future clinical 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