Alzheimer’s Disease: Protective Effects of Mycobacterium vaccae, a Soil-Derived Mycobacterium with Anti-Inflammatory and Anti-Tubercular Properties, on the Proteomic Profiles of Plasma and Cerebrospinal Fluid in Rats

2020 ◽  
Vol 78 (3) ◽  
pp. 965-987
Author(s):  
Kelsey M. Loupy ◽  
Thomas Lee ◽  
Cristian A. Zambrano ◽  
Ahmed I. Elsayed ◽  
Heather M. D’Angelo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Bacterial Infections ◽  
Cholesterol Metabolism ◽  
Male Rats ◽  
Interleukin 4 ◽  
Protective Effects ◽  
Mycobacterium Vaccae ◽  
Anti Inflammatory

Background: Alzheimer’s disease (AD) is an inflammatory neurodegenerative disease that may be associated with prior bacterial infections. Microbial “old friends” can suppress exaggerated inflammation in response to disease-causing infections or increase clearance of pathogens such as Mycobacterium tuberculosis, which causes tuberculosis (TB). One such “old friend” is Mycobacterium vaccae NCTC 11659, a soil-derived bacterium that has been proposed either as a vaccine for prevention of TB, or as immunotherapy for the treatment of TB when used alongside first line anti-TB drug treatment. Objective: The goal of this study was to use a hypothesis generating approach to explore the effects of M. vaccae on physiological changes in the plasma and cerebrospinal fluid (CSF). Methods: Liquid chromatography-tandem mass spectrometry-based proteomics were performed in plasma and CSF of adult male rats after immunization with a heat-killed preparation of M. vaccae NCTC 11659 or borate-buffered saline vehicle. Gene enrichment analysis and analysis of protein-protein interactions were performed to integrate physiological network changes in plasma and CSF. We used RT-qPCR to assess immune and metabolic gene expression changes in the hippocampus. Results: In both plasma and CSF, immunization with M. vaccae increased proteins associated with immune activation and downregulated proteins corresponding to lipid (including phospholipid and cholesterol) metabolism. Immunization with M. vaccae also increased hippocampal expression of interleukin-4 (IL-4) mRNA, implicating anti-inflammatory effects in the central nervous system. Conclusion: M. vaccae alters host immune activity and lipid metabolism. These data are consistent with the hypothesis that microbe-host interactions may protect against possible infection-induced, inflammation-related cognitive impairments.

scholarly journals Increased Cerebrospinal Fluid Production as a Possible Mechanism Underlying Caffeine's Protective Effect against Alzheimer's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Peter Wostyn ◽  
Debby Van Dam ◽  
Kurt Audenaert ◽  
Peter Paul De Deyn
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Late Onset ◽  
Senile Plaques ◽  
Protective Effects ◽  
Caffeine Consumption ◽  
Neuroprotective Effects ◽  
Csf Production

Alzheimer's disease (AD), the most common type of dementia among older people, is characterized by the accumulation of β-amyloid (Aβ) senile plaques and neurofibrillary tangles composed of hyperphosphorylated tau in the brain. Despite major advances in understanding the molecular etiology of the disease, progress in the clinical treatment of AD patients has been extremely limited. Therefore, new and more effective therapeutic approaches are needed. Accumulating evidence from human and animal studies suggests that the long-term consumption of caffeine, the most commonly used psychoactive drug in the world, may be protective against AD. The mechanisms underlying the suggested beneficial effect of caffeine against AD remain to be elucidated. In recent studies, several potential neuroprotective effects of caffeine have been proposed. Interestingly, a recent study in rats showed that the long-term consumption of caffeine increased cerebrospinal fluid (CSF) production, associated with the increased expression of Na+-K+ATPase and increased cerebral blood flow. Compromised function of the choroid plexus and defective CSF production and turnover, with diminished clearance of Aβ, may be one mechanism implicated in the pathogenesis of late-onset AD. If reduced CSF turnover is a risk factor for AD, then therapeutic strategies to improve CSF flow are reasonable. In this paper, we hypothesize that long-term caffeine consumption could exert protective effects against AD at least in part by facilitating CSF production, turnover, and clearance. Further, we propose a preclinical experimental design allowing evaluation of this hypothesis.

scholarly journals The Role of High-Density Lipoproteins in Reducing the Risk of Vascular Diseases, Neurogenerative Disorders, and Cancer

Cholesterol ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Donovan McGrowder ◽  
Cliff Riley ◽  
Errol Y. St. A. Morrison ◽  
Lorenzo Gordon
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Current Knowledge ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
High Density Lipoproteins ◽  
Protective Effects ◽  
Anti Oxidant ◽  
Anti Inflammatory

High-density lipoprotein (HDL) is one of the major carriers of cholesterol in the blood. It attracts particular attention because, in contrast with other lipoproteins, as many physiological functions of HDL influence the cardiovascular system in favourable ways unless HDL is modified pathologically. The functions of HDL that have recently attracted attention include anti-inflammatory and anti-oxidant activities. High anti-oxidant and anti-inflammatory activities of HDL are associated with protection from cardiovascular disease. Atheroprotective activities, as well as a functional deficiency of HDL, ultimately depend on the protein and lipid composition of HDL. Further, numerous epidemiological studies have shown a protective association between HDL-cholesterol and cognitive impairment. Oxidative stress, including lipid peroxidation, has been shown to be the mediator of the pathologic effects of numerous risk factors of Alzheimer's disease. Lifestyle interventions proven to increase HDL- cholesterol levels including “healthy” diet, regular exercise, weight control, and smoking cessation have also been shown to provide neuro-protective effects. This review will focus on current knowledge of the beneficial effects of HDL-cholesterol as it relates to cardiovascular diseases, breast and lung cancers, non-Hodgkin's lymphoma, as well as its neuroprotective potential in reducing the risk of Alzheimer's disease and dementia.

scholarly journals CNS expression of anti‐inflammatory cytokine interleukin‐4 attenuates Alzheimer's disease‐like pathogenesis in APP+PS1 bigenic mice

2010 ◽  
Vol 24 (8) ◽  
pp. 3093-3102 ◽  
Author(s):  
Tomomi Kiyota ◽  
Satoshi Okuyama ◽  
Russell J. Swan ◽  
Michael T. Jacobsen ◽  
Howard E. Gendelman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inflammatory Cytokine ◽  
Interleukin 4 ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine

scholarly journals Cerebrospinal fluid Aβ42 and fractalkine are associated with Parkinson’s disease with freezing of gait

2020 ◽  
Author(s):  
J. M. Hatcher-Martin ◽  
J.L. McKay ◽  
B. Sommerfeld ◽  
J.C. Howell ◽  
F. C. Goldstein ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Linear Models ◽  
Inflammatory Marker ◽  
Freezing Of Gait ◽  
Cross Sectional ◽  
Anti Inflammatory

AbstractObjectiveTo evaluate the association of Alzheimer’s disease-related and inflammation-related cerebrospinal fluid (CSF) markers with freezing of gait (FOG) in patients with Parkinson’s disease (PD).MethodThe study population included well-characterized PD patients with FOG (PD-FOG), without FOG (PD-NoFOG) and healthy controls (HC). CSF was collected using standard protocols. Three Alzheimer’s disease-related markers and 10 inflammation-related markers were measured in a Luminex 200 platform. Differences in marker expression across groups were evaluated with multivariate linear models.ResultsCSF was collected from PD-FOG (N=12), PD-NoFOG (N=20) and HC (N=11) for analysis. Age was not significantly different between the three groups. Duration of PD was not significantly different between the two PD groups. After adjusting for covariates and multiple comparisons, the anti-inflammatory marker, fractalkine, was significantly decreased in the PD groups compared to HC (P=0.022), and further decreased in PD-FOG compared to PD-NoFOG or HC (P=0.032). The Alzheimer’s disease-related protein, Aβ42, was increased in PD-FOG compared to PD-NoFOG or HC (P=0.004). p-Tau181 was also decreased in both PD groups compared to HC (P=0.010).ConclusionsWe found high levels of Aβ42 in PD-FOG patients and cross-sectional data which supports an increase over time from early to advanced state. We also found low levels of fractalkine which might suggest anti-inflammatory effect. This is the first time an association between fractalkine and FOG has been shown. Whether these changes are specific to FOG requires further exploration.

scholarly journals Curcumin Attenuated Neurotoxicity in Sporadic Animal Model of Alzheimer’s Disease

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 3011
Author(s):  
Ines ELBini-Dhouib ◽  
Raoudha Doghri ◽  
Amenallah Ellefi ◽  
Imen Degrach ◽  
Najet Srairi-Abid ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Histopathological Analysis ◽  
Protective Effects ◽  
Inflammatory Cytokine Production ◽  
Beneficial Effects ◽  
Model Of Alzheimer’S Disease ◽  
Natural Polyphenol ◽  
Anti Inflammatory

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases leading to dementia. Despite research efforts, currently there are no effective pharmacotherapeutic options for the prevention and treatment of AD. Recently, numerous studies highlighted the beneficial effects of curcumin (CUR), a natural polyphenol, in the neuroprotection. Especially, its dual antioxidant and anti-inflammatory properties attracted the interest of researchers. In fact, besides its antioxidant and anti-inflammatory properties, this biomolecule is not degraded in the intestinal tract. Additionally, CUR is able to cross the blood–brain barrier and could therefore to be used to treat neurodegenerative pathologies associated with oxidative stress, inflammation and apoptosis. The present study aimed to assess the ability of CUR to induce neuronal protective and/or recovery effects on a rat model of neurotoxicity induced by aluminum chloride (AlCl3), which mimics the sporadic form of Alzheimer’s disease. Our results showed that treatment with CUR enhances pro-oxidant levels, antioxidant enzymes activities and anti-inflammatory cytokine production and decreases apoptotic cells in AlCl3-exposed hippocampus rats. Additionally, histopathological analysis of hippocampus revealed the potential of CUR in decreasing the hallmarks in the AlCl3-induced AD. We also showed that CUR post-treatment significantly improved the behavioral, oxidative stress and inflammation in AlCl3-exposed rats. Taken together, our data presented CUR as a nutraceutical potential through its protective effects that are more interesting than recovery ones in sporadic model of AD.

Amyloid beta in the Cerebrospinal Fluid and the Blood as a Biomarker for Alzheimer's Disease

HAPS Educator ◽  
2015 ◽  
Vol 20 (1) ◽  
pp. 38-43
Author(s):  
Brie Paddock ◽  
Kimberly Canfield ◽  
Sarah Cooper
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Beta
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