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A team of researchers led by Julie Ribot and Luísa Lopes, from the Instituto de Medicina Molecular João Lobo Antunes, shows that elevated levels of a pro-inflammatory signaling protein released by immune cells in the brain meninges mediates early cognitive deficits in Alzheimer’s disease. These findings, published today in the scientific journal Cell Reports*, highlight the importance of a fine balance of the immune system for brain function.

Alzheimer’s disease is a neurodegenerative disorder characterized by cognitive deficits induced by synaptic dysfunction. Due to the lack of available treatments, it is crucial to understand the causes of the disease. Neuroinflammation has been linked to the etiology of the disease. Recently, the same group of researchers identified that a population of immune cells, gd T lymphocytes, resides in the brain meninges, a direct interface between the brain and the immune system. In healthy conditions, these cells are important for cognition. Now, they showed that the cognitive deficits observed in the early stages of Alzheimer’s disease are mediated by the release of IL-17, a pro-inflammatory molecule, by this population of cells. Using animal models, the researchers have observed that these early stage alterations are observed in females, highlighting the importance of sexual dimorphisms in disease progression. Importantly, the early stage cognitive deficits and synaptic dysfunction observed, were prevented when animals were treated with IL-17 neutralizing antibodies, suggesting that inflammation is driving early onset disease symptoms.

Understanding the mechanisms that lead to early development of Alzheimer’s disease is important to develop new therapeutic strategies.

Additionally, further studies could lead to the use of IL-17 as a biomarker of early stages, improving Alzheimer’s disease diagnosis.

*Helena C. Brigas, Miguel Ribeiro, Joana E. Coelho, Rui Gomes, Victoria Gomez-Murcia, Kevin Carvalho, Emilie Faivre, Sara Costa-Pereira, Julie Darrigues, Afonso Antunes de Almeida, Luc Buée, Jade Dunot, Hélène Marie, Paula A. Pousinha, David Blum, Bruno Silva-Santos, Luísa V. Lopes, Julie C. Ribot (2021). IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer’s disease. Cell Reports 36(9)109574.