Front Immunol. 2017 Mar 2;8:211. doi: 10.3389/fimmu.2017.00211. eCollection 2017.
NETosis in Alzheimer's Disease.
Abstract
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.
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.
KEYWORDS:
Alzheimer’s disease; blood-brain barrier; neuroinflammation; neutrophil extracellular traps; neutrophils- PMID:
- 28303140
- PMCID:
- PMC5332471
- DOI:
- 10.3389/fimmu.2017.00211
