Immune dysfunction and inflammation found to play significant roles in Alzheimer’s disease

Brain tissue analysis of an animal model has revealed the potential role of immune system dysfunction in the onset and progression of Alzheimer’s disease (AD).

Published April 15, 2025 in the Journal of Alzheimer’s Disease, the new study uses RNA sequencing to demonstrate a link between neuroinflammation, innate immune memory, and cellular plasticity to AD progression.

In combination with the established science about amyloid and tau proteins in Alzheimer’s, increasing evidence implicates glia-driven neuroinflammatory mechanisms as a potential cause and presents an opportunity to investigate potential treatments for AD. Emerging research positions AD as an innate autoimmune pathology, driven by maladaptive immune responses to various endogenous “triggering molecules,” such as amyloid-Beta and tau.

This study expands the current literature by evaluating whether epigenetically encoded innate immune memory (trained immunity) and cell trans-differentiation also contribute to the disease cascade.

“This study identifies a novel immunological axis in Alzheimer’s disease,” says Domenico Praticò, MD, the Scott Richards North Star Foundation Chair for Alzheimer’s Research, Professor of Neural Sciences and Founding Director of the Alzheimer’s Center at Temple (ACT), at the Lewis Katz School of Medicine at Temple University (LKSOM).

“The findings emphasize the roles of trained immunity and inflammation enhancement, which may initiate a sustained cycle of dysfunctional immune responses. This overactive immune response then promotes chronic neuroinflammation and cellular reprogramming, contributing to the onset and progression of this debilitating disease.”

Brain tissue analysis of an animal model has revealed the potential role of immune system dysfunction in the onset and progression of Alzheimer’s disease (AD).

Published April 15, 2025 in the Journal of Alzheimer’s Disease, the new study uses RNA sequencing to demonstrate a link between neuroinflammation, innate immune memory, and cellular plasticity to AD progression.

In combination with the established science about amyloid and tau proteins in Alzheimer’s, increasing evidence implicates glia-driven neuroinflammatory mechanisms as a potential cause and presents an opportunity to investigate potential treatments for AD. Emerging research positions AD as an innate autoimmune pathology, driven by maladaptive immune responses to various endogenous “triggering molecules,” such as amyloid-Beta and tau.

This study expands the current literature by evaluating whether epigenetically encoded innate immune memory (trained immunity) and cell trans-differentiation also contribute to the disease cascade.

“This study identifies a novel immunological axis in Alzheimer’s disease,” says Domenico Praticò, MD, the Scott Richards North Star Foundation Chair for Alzheimer’s Research, Professor of Neural Sciences and Founding Director of the Alzheimer’s Center at Temple (ACT), at the Lewis Katz School of Medicine at Temple University (LKSOM).

“The findings emphasize the roles of trained immunity and inflammation enhancement, which may initiate a sustained cycle of dysfunctional immune responses. This overactive immune response then promotes chronic neuroinflammation and cellular reprogramming, contributing to the onset and progression of this debilitating disease.”