P2-264: Oxysterols, Blood-Brain Barrier (BBB) and Alzheimer's Disease: in vitro studies on endothelial cells and pericytes

2011 ◽  
Vol 7 ◽  
pp. S396-S397
Author(s):  
Julien Saint-Pol ◽  
Elodie Vandenhaute ◽  
Marie-Christine Boucau ◽  
Lucie Dehouck ◽  
Roméo Cecchelli ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
In Vitro Studies ◽  
Brain Barrier ◽  
Blood Brain

In vitro transcytosis of Helicobacter pylori histidine-rich protein through gastric epithelial-like cells and the blood–brain barrier

2021 ◽  
Author(s):  
Takashi Iwasaki ◽  
Aiki Maruyama ◽  
Yurika Inui ◽  
Toshihiko Sakurai ◽  
Tsuyoshi Kawano
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Helicobacter Pylori ◽  
Disease Progression ◽  
Blood Brain Barrier ◽  
Gastric Epithelium ◽  
Brain Barrier ◽  
Blood Brain ◽  
H Pylori

Abstract Recent epidemiological studies have supported the correlation between Helicobacter pylori infection and the development of Alzheimer's disease. HpHpn, a histidine-rich H. pylori protein, forms amyloid-like oligomers; it may be a pathogenic factor for Alzheimer's disease progression. HpHpn may also be transported from the gastric epithelium to the brain. However, HpHpn is secreted from H. pylori on the outer surface of gastric epithelia; therefore, the hypothesized movement of HpHpn across the gastric epithelium to the blood remains controversial. Here, we found the HpHpn showed acidic pH-dependent cellular uptake and subsequent secretion in human gastric epithelial-like carcinoma cells. Furthermore, HpHpn exhibited in vitro permeability across the blood–brain barrier. Although further in vivo experiments are required, our findings suggest that in vitro transcytosis of HpHpn in gastric epithelial cells and the blood–brain barrier may provide new insights into the correlation between H. pylori infections and Alzheimer's disease progression.

Do Periodontal Pathogens or Associated Virulence Factors Have a Deleterious Effect on the Blood-Brain Barrier, Contributing to Alzheimer’s Disease?

2021 ◽  
pp. 1-17
Author(s):  
Mhd Ammar Kouki ◽  
Anna Barlach Pritchard ◽  
Jane Elizabeth Alder ◽  
StJohn Crean
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Virulence Factors ◽  
Current Knowledge ◽  
Brain Barrier ◽  
Periodontal Pathogens ◽  
Blood Brain

The central nervous system (CNS) is protected by a highly selective barrier, the blood-brain barrier (BBB), that regulates the exchange and homeostasis of bloodborne molecules, excluding xenobiotics. This barrier forms the first line of defense by prohibiting pathogens from crossing to the CNS. Aging and chronic exposure of the BBB to pathogens renders it permeable, and this may give rise to pathology in the CNS such as Alzheimer’s disease (AD). Researchers have linked pathogens associated with periodontitis to neuroinflammation and AD-like pathology in vivo and in vitro. Although the presence of periodontitis-associated bacteria has been linked to AD in several clinical studies as DNA and virulence factors were confirmed in brain samples of human AD subjects, the mechanism by which the bacteria traverse to the brain and potentially influences neuropathology is unknown. In this review, we present current knowledge about the association between periodontitis and AD, the mechanism whereby periodontal pathogens might provoke neuroinflammation and how periodontal pathogens could affect the BBB. We suggest future studies, with emphasis on the use of human in vitro models of cells associated with the BBB to unravel the pathway of entry for these bacteria to the CNS and to reveal the molecular and cellular pathways involved in initiating the AD-like pathology. In conclusion, evidence demonstrate that bacteria associated with periodontitis and their virulence factors are capable of inflecting damage to the BBB and have a role in giving rise to pathology similar to that found in AD.

scholarly journals BACE-1 is expressed in the blood–brain barrier endothelium and is upregulated in a murine model of Alzheimer’s disease

2015 ◽  
Vol 36 (7) ◽  
pp. 1281-1294 ◽  
Author(s):  
Kavi Devraj ◽  
Slobodan Poznanovic ◽  
Christoph Spahn ◽  
Gerhard Schwall ◽  
Patrick N Harter ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Mouse Brain Endothelial Cells ◽  
Primary Mouse ◽  
Β Amyloid ◽  
Bace 1

Endothelial cells of the blood–brain barrier form a structural and functional barrier maintaining brain homeostasis via paracellular tight junctions and specific transporters such as P-glycoprotein. The blood–brain barrier is responsible for negligible bioavailability of many neuroprotective drugs. In Alzheimer’s disease, current treatment approaches include inhibitors of BACE-1 (β-site of amyloid precursor protein cleaving enzyme), a proteinase generating neurotoxic β-amyloid. It is known that BACE-1 is highly expressed in endosomes and membranes of neurons and glia. We now provide evidence that BACE-1 is expressed in blood–brain barrier endothelial cells of human, mouse, and bovine origin. We further show its predominant membrane localization by 3D- dSTORM super-resolution microscopy, and by biochemical fractionation that further shows an abluminal distribution of BACE-1 in brain microvessels. We confirm its functionality in processing APP in primary mouse brain endothelial cells. In an Alzheimer’s disease mouse model we show that BACE-1 is upregulated at the blood–brain barrier compared to healthy controls. We therefore suggest a critical role for BACE-1 at the blood–brain barrier in β-amyloid generation and in vascular aspects of Alzheimer’s disease, particularly in the development of cerebral amyloid angiopathy.

scholarly journals Highly Stabilized Curcumin Nanoparticles Tested in an In Vitro Blood–Brain Barrier Model and in Alzheimer’s Disease Tg2576 Mice

2012 ◽  
Vol 15 (2) ◽  
pp. 324-336 ◽  
Author(s):  
Kwok Kin Cheng ◽  
Chin Fung Yeung ◽  
Shuk Wai Ho ◽  
Shing Fung Chow ◽  
Albert H. L. Chow ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Curcumin Nanoparticles ◽  
Blood Brain ◽  
Blood Brain Barrier Model ◽  
Barrier Model ◽  
Tg2576 Mice

scholarly journals Accelerated pericyte degeneration and blood–brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer’s disease

2015 ◽  
Vol 36 (1) ◽  
pp. 216-227 ◽  
Author(s):  
Matthew R Halliday ◽  
Sanket V Rege ◽  
Qingyi Ma ◽  
Zhen Zhao ◽  
Carol A Miller ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Late Onset ◽  
Density Lipoprotein ◽  
Brain Barrier ◽  
Lipoprotein Receptor ◽  
Apolipoprotein E4 ◽  
Blood Brain

The blood–brain barrier (BBB) limits the entry of neurotoxic blood-derived products and cells into the brain that is required for normal neuronal functioning and information processing. Pericytes maintain the integrity of the BBB and degenerate in Alzheimer’s disease (AD). The BBB is damaged in AD, particularly in individuals carrying apolipoprotein E4 ( APOE4) gene, which is a major genetic risk factor for late-onset AD. The mechanisms underlying the BBB breakdown in AD remain, however, elusive. Here, we show accelerated pericyte degeneration in AD APOE4 carriers >AD APOE3 carriers >non-AD controls, which correlates with the magnitude of BBB breakdown to immunoglobulin G and fibrin. We also show accumulation of the proinflammatory cytokine cyclophilin A (CypA) and matrix metalloproteinase-9 (MMP-9) in pericytes and endothelial cells in AD ( APOE4 > APOE3), previously shown to lead to BBB breakdown in transgenic APOE4 mice. The levels of the apoE lipoprotein receptor, low-density lipoprotein receptor-related protein-1 (LRP1), were similarly reduced in AD APOE4 and APOE3 carriers. Our data suggest that APOE4 leads to accelerated pericyte loss and enhanced activation of LRP1-dependent CypA–MMP-9 BBB-degrading pathway in pericytes and endothelial cells, which can mediate a greater BBB damage in AD APOE4 compared with AD APOE3 carriers.

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