Emerging Research Highlights the Role of Immune Dysfunction and Inflammation in Alzheimer's Disease

Recent studies using brain tissue analysis in animal models have shed light on the significant contribution of immune system dysfunction to the development and progression of Alzheimer's disease (AD). Published on April 15, 2025, in the Journal of Alzheimer's Disease, a comprehensive new study employs RNA sequencing techniques to explore the relationship between neuroinflammation, innate immune memory, and cellular plasticity in the context of AD.

The research integrates existing knowledge about amyloid plaques and tau proteins—well-known hallmarks of Alzheimer's—with emerging evidence pointing toward glia-driven neuroinflammatory mechanisms. These mechanisms are increasingly viewed as potential causal factors, offering new avenues for treatment development. Notably, recent findings suggest that AD may be characterized as an innate autoimmune disorder, where maladaptive immune responses are triggered by endogenous molecules such as amyloid-beta and tau.

Beyond traditional views, this study investigates whether epigenetically encoded innate immune memory—also known as trained immunity—and cellular trans-differentiation contribute to the disease cascade. The researchers propose a novel immunological axis in AD, emphasizing the roles of trained immunity and heightened inflammation. These responses could create a self-perpetuating cycle of immune dysregulation, fostering chronic neuroinflammation and reprogramming of neuronal and glial cells.

According to Dr. Domenico Praticò, a leading Alzheimer's researcher at Temple University, the findings highlight the importance of immune system dynamics in AD. "The exaggeration of immune responses initiates a sustained inflammatory cycle, which then promotes ongoing neurodegeneration and cellular reprogramming, contributing to the disease’s progression," he explains.

This expanded understanding of AD as an autoimmune-related, immune-driven pathology opens new possibilities for therapeutic interventions aimed at modulating neuroinflammation, immune memory, and cellular plasticity. By targeting these immune mechanisms, future treatments could potentially slow or prevent the disease's advancement.

For more detailed insights, the full study is available in the Journal of Alzheimer's Disease (2025), authored by Fatma Saaoud et al., discussing the concept of Alzheimer’s disease as an auto-innate immune disorder with potential cell trans-differentiation and enhanced trained immunity in a 3xTg-AD mouse model.