In a groundbreaking merger of immunotherapy and neurodegenerative disease research, scientists from Washington University School of Medicine and the Weizmann Institute of Science have harnessed the power of chimeric antigen receptor (CAR) T cell technology to combat Alzheimer’s disease in a novel and promising way. This pioneering study, recently published in the Proceedings of the National Academy of Sciences, marks the first instance of CAR-T cells being employed against a neurodegenerative disorder, signaling a radical shift in therapeutic approaches to brain diseases traditionally deemed intractable.
CAR-T cell therapy, previously heralded for its success in targeting certain cancers by genetically engineering a patient’s own immune cells to seek and destroy malignant cells, has now been precisely tailored to attack amyloid beta plaques — protein aggregates widely recognized as a pathological hallmark of Alzheimer’s disease. By modifying CD4+ T cells to recognize these rogue protein accumulations, the research team set out to demonstrate the therapeutic potential of this immune strategy in the brain, an organ notoriously protected by the blood-brain barrier and immune privilege.
The impetus for this innovation stems from emerging insights into the relationship between the immune system and neurological health. Jonathan Kipnis, a leading expert in neuroimmunology and co-senior author of the study, emphasizes how recent discoveries of meningeal lymphatics—vascular structures that facilitate communication between the brain and peripheral immunity—have revolutionized our understanding of immune-brain interactions. By tapping into these pathways, the research team has managed to direct immunological weapons within the central nervous system to combat neurodegenerative pathology in vivo.
In the experimental design, CD4+ T cells extracted from healthy mice were genetically reprogrammed to express chimeric antigen receptors specific for amyloid beta. These engineered immune cells were then infused back into mouse models carrying genetic mutations responsible for amyloid plaque formation, mimicking the pathophysiology seen in Alzheimer’s patients. Following a regimen of three injections spaced ten days apart, significant reductions in cerebral amyloid burden were observed, accompanied by markers indicative of improved brain tissue health.
The success of these CAR-T cells extended beyond plaque clearance. Mice treated with the engineered immune cells exhibited decreased activation of microglia and astrocytes—glial cells that, when excessively activated in Alzheimer’s, contribute to neuroinflammation and neuronal damage. The dampening of this neuroinflammatory response underscores the dual action of engineered CAR-T cells: not only targeting the toxic protein deposits but also modulating the central nervous system’s immune environment in a manner that favors tissue repair and homeostasis.
This multidisciplinary venture involved collaboration with immunologist Ido Amit of the Weizmann Institute, whose expertise in immune cell engineering proved instrumental in designing CAR constructs specifically attuned to amyloid beta. The initiative exemplifies how international cooperative frameworks can accelerate innovation, as demonstrated by the collaborative research partnership launched between Washington University and the Weizmann Institute just a year prior to this study’s publication.
This study serves as the first stepping stone in a potentially broad application of CAR-T cell technology in neurodegenerative diseases. Pavle Boskovic, the study’s first author, expressed optimism regarding extending this approach beyond Alzheimer’s, highlighting the possibility of addressing inflammatory pathways common to disorders such as amyotrophic lateral sclerosis and Parkinson’s disease. The adaptability of CAR-T cells renders them uniquely suited for such exploratory therapeutics, given their programmable antigen specificity and modulatory capabilities.
Crucial to the translation of this therapy from mouse models to human application will be a comprehensive understanding of how these engineered T cells navigate the brain’s complex immunological milieu. Future research will need to dissect the mechanisms underlying the observed neuroprotective effects and optimize cell dosing and delivery methods to mitigate potential adverse immune reactions, such as neurotoxicity or off-target effects.
Supporting this transformative work, the Carol and Gene Ludwig Initiative in Neuroimmunology Research has provided vital funding to propel investigations into the interplay between immune-mediated mechanisms and neurodegeneration. Such investment underscores a growing recognition of neuroimmunology as a fertile frontier for developing novel therapies for Alzheimer’s and related disorders, where current treatment options remain limited.
While this innovative therapy demonstrates potent efficacy in animal models, challenges remain before clinical translation. The intricacies of human neuroimmunology and the heterogeneity of Alzheimer’s disease pathology necessitate rigorous clinical evaluation. Nonetheless, these findings set the stage for a paradigm shift, where immunotherapy transcends its oncological roots to become a versatile platform against debilitating brain diseases.
This pioneering research not only offers hope for treating Alzheimer’s disease but also heralds a new era in neuroscience, where the immune system’s capacity can be engineered and directed with precision to promote brain health. As the scientific community rallies toward combating neurodegeneration, CAR-T cell therapy stands out as a beacon of innovation, representing an intersection of molecular biology, immunology, and neurology that could redefine therapeutic boundaries.
Through this study, the scientific landscape advances toward a future where engineered immune cells may become a mainstay in the arsenal against neurodegeneration, delivering targeted interventions that prevent or even reverse the progression of diseases that have long eluded effective treatment.
Subject of Research: Animals
Article Title: Chimeric antigen receptor (CAR) CD4 T-cells for Alzheimer’s disease
News Publication Date: 9-Feb-2026
References:
Boskovic P, Shalita R, Gao W, Vernon H, Deng YL, Colonna M, Majzner RG, Amit I, Kipnis J. Chimeric antigen receptor (CAR) CD4 T-cells for Alzheimer’s disease. PNAS. February 9, 2026.
Keywords: Neurodegenerative diseases
