scholarly journals Intracerebral GM-CSF contributes to transendothelial monocyte migration in APP/PS1 Alzheimer’s disease mice

2016 ◽  
Vol 36 (11) ◽  
pp. 1978-1991 ◽  
Author(s):  
De S Shang ◽  
Yi M Yang ◽  
Hu Zhang ◽  
Li Tian ◽  
Jiu S Jiang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Colony Stimulating Factor ◽  
Blood Brain ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
The Brain ◽  
Stimulating Factor

Although tight junctions between human brain microvascular endothelial cells in the blood–brain barrier prevent molecules or cells in the bloodstream from entering the brain, in Alzheimer’s disease, peripheral blood monocytes can “open” these tight junctions and trigger subsequent transendothelial migration. However, the mechanism underlying this migration is unclear. Here, we found that the CSF2RB, but not CSF2RA, subunit of the granulocyte-macrophage colony-stimulating factor receptor was overexpressed on monocytes from Alzheimer’s disease patients. CSF2RB contributes to granulocyte-macrophage colony-stimulating factor-induced transendothelial monocyte migration. Granulocyte-macrophage colony-stimulating factor triggers human brain microvascular endothelial cells monolayer tight junction disassembly by downregulating ZO-1 expression via transcription modulation and claudin-5 expression via the ubiquitination pathway. Interestingly, intracerebral granulocyte-macrophage colony-stimulating factor blockade abolished the increased monocyte infiltration in the brains of APP/PS1 Alzheimer’s disease model mice. Our results suggest that in Alzheimer’s disease patients, high granulocyte-macrophage colony-stimulating factor levels in the brain parenchyma and cerebrospinal fluid induced blood–brain barrier opening, facilitating the infiltration of CSF2RB-expressing peripheral monocytes across blood–brain barrier and into the brain. CSF2RB might be useful as an Alzheimer’s disease biomarker. Thus, our findings will help to understand the mechanism of monocyte infiltration in Alzheimer’s disease pathogenesis.

scholarly journals Probable Causes of Alzheimer’s Disease

Sci ◽  
2021 ◽  
Vol 3 (1) ◽  
pp. 16
Author(s):  
James David Adams
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lactic Acid ◽  
Blood Brain Barrier ◽  
Transient Receptor Potential ◽  
Brain Barrier ◽  
Folate Intake ◽  
Blood Brain ◽  
Age Related ◽  
The Brain

A three-part mechanism is proposed for the induction of Alzheimer’s disease: (1) decreased blood lactic acid; (2) increased blood ceramide and adipokines; (3) decreased blood folic acid. The age-related nature of these mechanisms comes from age-associated decreased muscle mass, increased visceral fat and changes in diet. This mechanism also explains why many people do not develop Alzheimer’s disease. Simple changes in lifestyle and diet can prevent Alzheimer’s disease. Alzheimer’s disease is caused by a cascade of events that culminates in damage to the blood–brain barrier and damage to neurons. The blood–brain barrier keeps toxic molecules out of the brain and retains essential molecules in the brain. Lactic acid is a nutrient to the brain and is produced by exercise. Damage to endothelial cells and pericytes by inadequate lactic acid leads to blood–brain barrier damage and brain damage. Inadequate folate intake and oxidative stress induced by activation of transient receptor potential cation channels and endothelial nitric oxide synthase damage the blood–brain barrier. NAD depletion due to inadequate intake of nicotinamide and alterations in the kynurenine pathway damages neurons. Changes in microRNA levels may be the terminal events that cause neuronal death leading to Alzheimer’s disease. A new mechanism of Alzheimer’s disease induction is presented involving lactic acid, ceramide, IL-1β, tumor necrosis factor α, folate, nicotinamide, kynurenine metabolites and microRNA.

Recent Advances in Targeted Drug Delivery Approaches using Lipidic and Polymeric Nanocarriers for the management of Alzheimer’s Disease

2021 ◽  
Vol 27 ◽  
Author(s):  
Dhara Lakdawala ◽  
Md Abdur Rashid ◽  
Farhan Jalees Ahmad
Keyword(s):  
Alzheimer’S Disease ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Targeted Drug Delivery ◽  
Brain Barrier ◽  
Polymeric Nanocarriers ◽  
Blood Brain ◽  
Targeted Drug ◽  
The Brain

: Drug delivery to the brain has remained a significant challenge in treating neurodegenerative disorders such as Alzheimer's disease due to the presence of the blood-brain barrier, which primarily obstructs the access of drugs and biomolecules into the brain. Several methods to overcome the blood-brain barrier have been employed, such as chemical disruption, surgical intervention, focused ultrasound, intranasal delivery and using nanocarriers. Nanocarrier systems remain the method of choice and have shown promising results over the past decade to achieve better drug targeting. Polymeric nanocarriers and lipidic nanoparticles act as a carrier system providing better encapsulation of drugs, site-specific delivery, increased bioavailability and sustained release of drugs. The surface modifications and functionalization of these nanocarrier systems have greatly facilitated targeted drug delivery. The safety and efficacy of these nanocarrier systems have been ascertained by several in vitro and in vivo models. In the present review, we have elaborated on recent developments of nanoparticles as a drug delivery system for Alzheimer's disease, explicitly focusing on polymeric and lipidic nanoparticles.

Amyloid β Protein Deposition in Osteopetrotic (op/op) Mice Is Reduced by Injections of Macrophage Colony Stimulating Factor

2005 ◽  
Vol 33 (6) ◽  
pp. 654-660 ◽  
Author(s):  
T Kawata ◽  
K Tsutsui ◽  
S Kohno ◽  
M Kaku ◽  
T Fujita ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Microglial Cell ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Colony Stimulating Factor ◽  
Β Protein ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

The deposition of amyloid β (Aβ) protein is a neuropathological change that characterizes Alzheimer's disease. Animals with the osteopetrosis (op/op) mutation suffer from a general skeletal sclerosis, a significantly reduced number of macrophages and osteoclasts in various tissues, and have no systemic macrophage colony stimulating factor (M-CSF). This study examined the effect that M-CSF injections had on Aβ deposition and microglial cell distribution in the brains of normal and op/op mice. Aβ-positive plaques were detected in the cerebral cortex of op/op mice, but not in normal mice. M-CSF reduced the numbers of Aβ-positive plaques in op/op mice. The microglial cell population was reduced in op/op mice compared with normal mice, and M-CSF increased the numbers to 65.8% of that observed in normal mice. Our results suggest that a clearer understanding of the role that microglial cells play in Aβ deposition may help determine the mechanisms involved in the pathogenesis of Alzheimer's disease.

scholarly journals Time to test antibacterial therapy in Alzheimer’s disease

Brain ◽  
2019 ◽  
Author(s):  
Francesco Panza ◽  
Madia Lozupone ◽  
Vincenzo Solfrizzi ◽  
Mark Watling ◽  
Bruno P Imbimbo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Blood Brain Barrier ◽  
Amyloid Β ◽  
The Other ◽  
Brain Barrier ◽  
The Past ◽  
Blood Brain ◽  
The Brain

Abstract Alzheimer’s disease is associated with cerebral accumulation of amyloid-β peptide and hyperphosphorylated tau. In the past 28 years, huge efforts have been made in attempting to treat the disease by reducing brain accumulation of amyloid-β in patients with Alzheimer’s disease, with no success. While anti-amyloid-β therapies continue to be tested in prodromal patients with Alzheimer’s disease and in subjects at risk of developing Alzheimer’s disease, there is an urgent need to provide therapeutic support to patients with established Alzheimer’s disease for whom current symptomatic treatment (acetylcholinesterase inhibitors and N-methyl d-aspartate antagonist) provide limited help. The possibility of an infectious aetiology for Alzheimer’s disease has been repeatedly postulated over the past three decades. Infiltration of the brain by pathogens may act as a trigger or co-factor for Alzheimer’s disease, with Herpes simplex virus type 1, Chlamydia pneumoniae, and Porphyromonas gingivalis being most frequently implicated. These pathogens may directly cross a weakened blood–brain barrier, reach the CNS and cause neurological damage by eliciting neuroinflammation. Alternatively, pathogens may cross a weakened intestinal barrier, reach vascular circulation and then cross blood–brain barrier or cause low grade chronic inflammation and subsequent neuroinflammation from the periphery. The gut microbiota comprises a complex community of microorganisms. Increased permeability of the gut and blood–brain barrier induced by microbiota dysbiosis may impact Alzheimer’s disease pathogenesis. Inflammatory microorganisms in gut microbiota are associated with peripheral inflammation and brain amyloid-β deposition in subjects with cognitive impairment. Oral microbiota may also influence Alzheimer’s disease risk through circulatory or neural access to the brain. At least two possibilities can be envisaged to explain the association of suspected pathogens and Alzheimer’s disease. One is that patients with Alzheimer’s disease are particularly prone to microbial infections. The other is that microbial infection is a contributing cause of Alzheimer’s disease. Therapeutic trials with antivirals and/or antibacterials could resolve this dilemma. Indeed, antiviral agents are being tested in patients with Alzheimer’s disease in double-blind placebo-controlled studies. Although combined antibiotic therapy was found to be effective in animal models of Alzheimer’s disease, antibacterial drugs are not being widely investigated in patients with Alzheimer’s disease. This is because it is not clear which bacterial populations in the gut of patients with Alzheimer’s disease are overexpressed and if safe, selective antibacterials are available for them. On the other hand, a bacterial protease inhibitor targeting P. gingivalis toxins is now being tested in patients with Alzheimer’s disease. Clinical studies are needed to test if countering bacterial infection may be beneficial in patients with established Alzheimer’s disease.

scholarly journals Granulocyte-macrophage colony-stimulating factor neuroprotective activities in Alzheimer’s disease mice

2018 ◽  
Vol 319 ◽  
pp. 80-92 ◽  
Author(s):  
Tomomi Kiyota ◽  
Jatin Machhi ◽  
Yaman Lu ◽  
Bhagyalaxmi Dyavarshetty ◽  
Maryam Nemati ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor
Sign in / Sign up

Export Citation Format

Share Document