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A role for vascular inflammation and neutrophil trafficking in th | 49167

Journal of Neurology & Neurophysiology

ISSN - 2155-9562

A role for vascular inflammation and neutrophil trafficking in the pathogenesis of Alzheimers disease

10th International Conference on Neuroscience and Neurochemistry and 6th International Conference on Vascular Dementia

February 27-March 01, 2017

Gabriela Constantin

University of Verona, Italy

Posters & Accepted Abstracts: J Neurol Neurophysiol

Abstract :

A dysfunctional blood-brain-barrier and vascular inflammation have been implicated in the pathogenesis of Alzheimerâ??s disease (AD). However, the role of leukocyte trafficking mechanisms in AD is unclear. Using mice with five familial AD (5xFAD) mutations presenting amyloid pathology, and 3xTg-AD mice with both amyloid and tau pathology, we found increased expression of vascular adhesion molecules in areas with amyloid deposits. Surprisingly, we found an increased accumulation of neutrophils in the brain of AD mice with an infiltration peak at the onset of cognitive deficit. Migrating neutrophils released IL-17 and neutrophil extracellular traps (NETs) and established contacts with glial cells. Two-photon microscopy experiments also showed that integrins and selectins control neutrophil extravasation and intraparenchymal motility. Neutrophil depletion or the inhibition of neutrophil trafficking improved memory function, reduced microglial activation, amyloid deposition, tau phosphorylation and synaptic dysfunction compared to control animals. Notably, restoration of cognitive function in mice with temporary inhibition of neutrophil function during early disease was maintained at later time points in aged animals. To understand the relevance of our data in humans, we analyzed human cortical brain samples from subjects with AD. In Alzheimer's patients, neutrophils adhered and spread inside brain venules or migrated into the parenchyma and released NETs in larger numbers than in control subjects. Current Alzheimerâ??s disease therapies provide only temporary improvement and marginally reduce the rate of cognitive decline. Therefore, we propose that targeting vascular inflammation and leukocyte trafficking may represent a new therapeutic strategy in AD.

Biography :

Email: gabriela.constantin@univr.it

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