The blood-brain barrier in Alzheimer's disease

By Elena Zenaro, G. Piacentino, Gabriela Constantin. Neurobiology of Disease, 2017

697 citations recorded by the source corpus.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by the pathological accumulation of amyloid beta (Aβ) peptides and neurofibrillary tangles containing hyperphosphorylated neuronal tau protein. AD pathology is also characterized by chronic brain inflammation, which promotes disease pathogenesis. In this context, the blood-brain barrier (BBB), a highly specialized endothelial cell membrane that lines cerebral microvessels, represents the interface between neural cells and circulating cells of the immune system. The BBB thus plays a key role in the generation and maintenance of chronic inflammation during AD. The BBB operates within the neurovascular unit (NVU), which includes clusters of glial cells, neurons and pericytes. The NVU becomes dysfunctional during AD, and each of its components may undergo functional changes that contribute to neuronal injury and cognitive deficit. In transgenic animals with AD-like pathology, recent studies have shown that circulating leukocytes migrate through the activated brain endothelium when certain adhesion molecules are expressed, penetrating into the brain parenchyma, interacting with the NVU components and potentially affecting their structural integrity and functionality. Therefore, migrating immune system cells in cerebral vessels act in concert with the modified BBB and may be integrated into the dysfunctional NVU. Notably, blocking the adhesion mechanisms controlling leukocyte–endothelial interactions inhibits both Aβ deposition and tau hyperphosphorylation, and reduces memory loss in AD models. The characterization of molecular mechanisms controlling vascular inflammation and leukocyte trafficking could therefore help to determine the basis of BBB dysfunction during AD and may lead to the development of new therapeutic approaches.

Subfields: Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/a706b794690cf2160499b05f294881ce9a9b3c2d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Neurology

1. Gabriela Constantin
2. D. Agalliu

In Physiology

1. Gabriela Constantin
2. Dan Xiao
3. Weifeng Zhang
4. Haibin Xia
5. Q. Mao
6. D. Agalliu

Citations in the corpus

• Functional morphology of the blood-brain barrier in health and disease (2018, positive): “Over the years, several in vivo imaging methodologies have been developed to measure the integrity of the BBB. Magnetic resonance imaging (MRI), computed tomography (CT)/ Acta Neuropathol.”
• Role of neuroinflammation in neurodegeneration development (2023, background): “In mouse model of AD and AD patients, BBB benefits the clearance of Aβ aggregates through the efflux of amyloid from the brain by dedicated transporters, such as LRP1 (lipoprotein receptor-related protein-1) and P-glycoprotein,(136,137) while vascular risk factors induced microvascular inflammation ”