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Biological Chemistry

Connecting Alzheimer’s With Inflammation

Antibody blocks immune response, reducing toxic peptide in brains of mice with disease symptoms and improving their cognition

by Lauren K. Wolf
December 10, 2012 | A version of this story appeared in Volume 90, Issue 50

An antibody that’s being used to treat psoriasis and is in clinical trials for Crohn’s disease and multiple sclerosis can now add Alzheimer’s disease to the list of conditions for which it shows promise (Nat. Med., DOI: 10.1038/nm.2965). The Y-shaped macromolecule binds and neutralizes p40, a subunit of two cell-signaling proteins called interleukins that regulate tissue inflammation via the immune system. A research team led by Burkhard Becher of the University of Zurich and Frank L. Heppner of Germany’s Charité University Hospital has demonstrated that, when administered to mice with Alzheimer’s symptoms, a p40-blocking antibody improves the rodents’ short-term memory. It also reduces the amount of aggregated amyloid-β—the hallmark peptide of Alzheimer’s—in their brains. Before testing the antibody on the mice, the team established the p40-Alzheimer’s connection by genetically engineering a group of mice to have disease symptoms but to also lack p40. These rodents had about 65% less amyloid-β in their brains than mice that had only Alzheimer’s symptoms. This study, the researchers write, establishes “a pathogenic contribution of the immune system in Alzheimer’s.”

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