Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive deterioration of cognitive functions. Its neuropathological features include amyloid-β (Aβ) accumulation, the formation of neurofibrillary tangles, and the loss of neurons and synapses. Neuroinflammation is a well-established feature of AD pathogenesis, and a better understanding of its mechanisms could facilitate the development of new therapeutic approaches. Recent studies in transgenic mouse models of AD have shown that neutrophils adhere to blood vessels and migrate inside the parenchyma. Moreover, studies in human AD subjects have also shown that neutrophils adhere and spread inside brain vessels and invade the parenchyma, suggesting these cells play a role in AD pathogenesis. Indeed, neutrophil depletion and the therapeutic inhibition of neutrophil trafficking, achieved by blocking LFA-1 integrin in AD mouse models, significantly reduced memory loss and the neuropathological features of AD. We observed that neutrophils release neutrophil extracellular traps (NETs) inside blood vessels and in the parenchyma of AD mice, potentially harming the blood–brain barrier and neural cells. Furthermore, confocal microscopy confirmed the presence of NETs inside the cortical vessels and parenchyma of subjects with AD, providing more evidence that neutrophils and NETs play a role in AD-related tissue destruction. The discovery of NETs inside the AD brain suggests that these formations may exacerbate neuro-inflammatory processes, promoting vascular and parenchymal damage during AD. The inhibition of NET formation has achieved therapeutic benefits in several models of chronic inflammatory diseases, including autoimmune diseases affecting the brain. Therefore, the targeting of NETs may delay AD pathogenesis and offer a novel approach for the treatment of this increasingly prevalent disease.
NETosis in Alzheimer’s Disease
E. Pietronigro,V. della Bianca,Elena Zenaro,G. Constantin
Published 2017 in Frontiers in Immunology
ABSTRACT
PUBLICATION RECORD
- Publication year
2017
- Venue
Frontiers in Immunology
- Publication date
2017-03-02
- Fields of study
Biology, Medicine
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
CONCEPTS
- alzheimer’s disease
A neurodegenerative disorder characterized by progressive cognitive decline and the brain pathology discussed in this abstract.
Aliases: AD
- blood-brain barrier
The vascular barrier separating the bloodstream from brain tissue, mentioned here as a structure that may be harmed by neutrophil extracellular traps.
Aliases: BBB
- blood vessels
The vascular structures in the brain where neutrophils and neutrophil extracellular traps are observed in this abstract.
- lfa-1 integrin
A leukocyte adhesion molecule referenced as a target whose blockade can inhibit neutrophil trafficking in Alzheimer’s disease models.
Aliases: lymphocyte function-associated antigen 1
- neuroinflammation
Inflammatory processes in the nervous system that are discussed here as a potential consequence of neutrophil extracellular traps in Alzheimer’s disease.
- neutrophil extracellular traps
Web-like structures released by neutrophils that consist of chromatin and associated proteins and are examined here in brain vessels and tissue.
Aliases: NETs
- neutrophils
Innate immune cells that can adhere to vessels, migrate into brain tissue, and release extracellular traps in the disease context discussed here.
- parenchyma
The functional brain tissue outside blood vessels where neutrophils and neutrophil extracellular traps are reported to appear in this abstract.