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Article Dans Une Revue Cell Reports Année : 2021

IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer’s disease

Luc Buée

Résumé

Neuroinflammation in patients with Alzheimer's disease (AD) and related mouse models has been recognized for decades, but the contribution of the recently described meningeal immune population to AD pathogenesis remains to be addressed. Here, using the 3xTg-AD model, we report an accumulation of interleukin-17 (IL-17)-producing cells, mostly γδ T cells, in the brain and the meninges of female, but not male, mice, concomitant with the onset of cognitive decline. Critically, IL-17 neutralization into the ventricles is sufficient to prevent short-term memory and synaptic plasticity deficits at early stages of disease. These effects precede blood-brain barrier disruption and amyloid-beta or tau pathology, implying an early involvement of IL-17 in AD pathology. When IL-17 is neutralized at later stages of disease, the onset of short-memory deficits and amyloidosis-related splenomegaly is delayed. Altogether, our data support the idea that cognition relies on a finely regulated balance of "inflammatory" cytokines derived from the meningeal immune system.

Domaines

Neurobiologie
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Origine : Publication financée par une institution

Dates et versions

inserm-03366653 , version 1 (05-10-2021)

Identifiants

Citer

Helena Brigas, Miguel Ribeiro, Joana Coelho, Rui Gomes, Victoria Gomez-Murcia, et al.. IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer’s disease. Cell Reports, 2021, 36 (9), pp.109574. ⟨10.1016/j.celrep.2021.109574⟩. ⟨inserm-03366653⟩
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