Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Zenaro, E; Pietronigro, E; Della Bianca, V; Piacentino, G; Marongiu, L; Budui, S; Turano, E; Rossi, B; Angiari, S; Dusi, S; Montresor, A; Carlucci, T; Nanì, S; Tosadori, G; Calciano, L; Catalucci, D; Berton, G; Bonetti, B; Constantin, G.
Neutrophils promote Alzheimer's disease-like pathology and cognitive decline via LFA-1 integrin.
Nat Med. 2015; 21(8): 880-886.
Doi: 10.1038/nm.3913
Web of Science
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
- Angiari Stefano
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Inflammation is a pathological hallmark of Alzheimer's disease, and innate immune cells have been shown to contribute to disease pathogenesis. In two transgenic models of Alzheimer's disease (5xFAD and 3xTg-AD mice), neutrophils extravasated and were present in areas with amyloid-β (Aβ) deposits, where they released neutrophil extracellular traps (NETs) and IL-17. Aβ42 peptide triggered the LFA-1 integrin high-affinity state and rapid neutrophil adhesion to integrin ligands. In vivo, LFA-1 integrin controlled neutrophil extravasation into the CNS and intraparenchymal motility. In transgenic Alzheimer's disease models, neutrophil depletion or inhibition of neutrophil trafficking via LFA-1 blockade reduced Alzheimer's disease-like neuropathology and improved memory in mice already showing cognitive dysfunction. Temporary depletion of neutrophils for 1 month at early stages of disease led to sustained improvements in memory. Transgenic Alzheimer's disease model mice lacking LFA-1 were protected from cognitive decline and had reduced gliosis. In humans with Alzheimer's disease, neutrophils adhered to and spread inside brain venules and were present in the parenchyma, along with NETs. Our results demonstrate that neutrophils contribute to Alzheimer's disease pathogenesis and cognitive impairment and suggest that the inhibition of neutrophil trafficking may be beneficial in Alzheimer's disease.
- Find related publications in this database (using NLM MeSH Indexing)
- Alzheimer Disease - etiology
- Alzheimer Disease - pathology
- Amyloid beta-Peptides - physiology
- Animals -
- Cell Adhesion -
- Cell Movement -
- Cognition Disorders - etiology
- Extracellular Traps -
- Humans -
- Interleukin-17 - biosynthesis
- Lymphocyte Function-Associated Antigen-1 - physiology
- Mice -
- Mice, Inbred C57BL -
- Mice, Transgenic -
- Neutrophils - physiology
- Peptide Fragments - physiology