Research press release


Nature Medicine

Targeting inflammation improves Alzheimer's disease



Frank L Heppner、Burkhard Becherたちは、脳のニューロンではない常在細胞(神経膠細胞と呼ばれる)がIL-12、IL-23や共通するサブユニットIL-12/23p40を放出していること、人為的にADを発症させたマウスの脳ではこれらの濃度が上昇してることを発見した。これらのサイトカインやこれらに共通する受容体のいずれかが欠失したマウスでは、ADに似た症状が軽減される。治療として、病気の初期に、あるいは病気の確定後に、共通するサブユニットIL-12/23p40に特異的なマウス抗体を投与すると症状が緩和し、認知課題において記憶が改善する。


A class of antibodies that target a specific pro-inflammatory cell-signaling protein (termed IL-12/23p40) and are used to treat psoriasis also show beneficial effects in mouse models of Alzheimer's disease (AD), according to a study published online this week in Nature Medicine.

Increased inflammation is thought to be both a cause and consequence of Alzheimer's disease. Although the pro-inflammatory cell-signaling proteins (or, cytokines) interleukin-12 (IL-12) and IL-23-both of which share the subunit IL-12/23p40-drive autoimmune diseases, it remains unclear whether they contribute to AD pathogenesis.

Frank L. Heppner, Burkhard Becher, and colleagues found that IL-12, IL-23 and the shared subunit IL-12/23p40 are released by non-neuronal resident cells of the brain, called glia, and are detected at elevated levels in the brains of mice engineered to develop AD. Mice lacking each of these cytokines or a shared receptor show reduced AD-like pathology. Therapeutically, when the authors gave the mice antibodies specific for the shared IL-12/23p40 subunit either early on or after disease is established, they found that there was reduced pathology and improved memory in cognitive tasks.

Moreover, the clinical relevance of these findings is bolstered by data from individuals with AD, showing a correlation between IL-12/23p40 levels in the cerebrospinal fluid and cognitive performance.

doi: 10.1038/nm.2965


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