What question did this study set out to answer?

To determine whether the adaptive immune system regulates Alzheimer's disease pathogenesis and modulates microglial behavior.

February 16, 2016Proceedings of the National Academy of SciencesOpen Access

The adaptive immune system restrains Alzheimer’s disease pathogenesis by modulating microglial function

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Authors

SMSamuel E. MarshBoston Children's Hospital EAEdsel M. AbudScripps Health ALAnita LakatosUniversity of California, Irvine

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Implication

Preclinical study demonstrates that adaptive immune deficiency accelerates amyloid pathology in transgenic mice, indicating a protective role for T and B cells.

Key Points

To determine whether the adaptive immune system regulates Alzheimer's disease pathogenesis and modulates microglial behavior.
Generated an immune-deficient Alzheimer's mouse model (Rag-5xfAD) lacking T, B, and natural killer (NK) cells to compare against immune-intact 5xfAD controls.
Assessed brain gene expression, microglial activation phenotypes, cytokine production, and phagocytic activity, including in vitro and in vivo preimmune IgG treatments.
Conducted bone marrow transplantation experiments in Rag-5xfAD mice to reconstitute the missing adaptive immune cell populations.
Rag-5xfAD mice exhibited a greater than twofold increase in beta-amyloid (Aβ) pathology alongside exacerbated neuroinflammation, increased cytokine production, and impaired microglial phagocytosis.
Treatment of Rag-5xfAD mice or isolated microglia with preimmune nonamyloid-reactive IgG restored microglial phagocytic capacity and enhanced Aβ clearance.
Bone marrow transplantation restoring adaptive immune cells in Rag-5xfAD mice dramatically attenuated Alzheimer's disease pathology.

Cite This Study

Marsh et al. (2016) studied this question.

synapsesocial.com/papers/69d73f5faa68b335b4f30b4f https://doi.org/10.1073/pnas.1525466113

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Implication

Preclinical study demonstrates that adaptive immune deficiency accelerates amyloid pathology in transgenic mice, indicating a protective role for T and B cells.

The adaptive immune system restrains Alzheimer’s disease pathogenesis by modulating microglial function

Discussion

Member takes

Implication

Key Points

Cite This Study

The adaptive immune system restrains Alzheimer’s disease pathogenesis by modulating microglial function

Discussion

Member takes

Implication

Key Points

Cite This Study

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