scholarly journals Dielectric Constant and Conductivity of Blood Plasma: Possible Novel Biomarkers for Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Ernest Dallé ◽  
Musa V. Mabandla ◽  
William M. U. Daniels
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dielectric Constant ◽  
Blood Plasma ◽  
Clinical Symptoms ◽  
Dorsal Hippocampus ◽  
Dependent Manner ◽  
Model Of Alzheimer’S Disease ◽  
Novel Biomarkers ◽  
New Treatments

Alzheimer’s disease is a complex debilitating neurodegenerative disease for which there is no cure. The lack of reliable biomarkers for Alzheimer’s disease has made the evaluation of the efficacy of new treatments difficult and reliant on only clinical symptoms. In an aged population where cognitive function may be deteriorating for other reasons, the dependence on clinical symptoms is also unreliable. However, it is well established that infusion of β-amyloid into the dorsal hippocampus of rats leads to cognitive impairment in a rat model of Alzheimer’s disease. Moreover, the blood plasma of β-amyloid-lesioned rats exhibits a distinct variation of the dielectric constant and conductivity when compared to that of normal rats in a time-dependent manner. These two electric parameters of blood plasma may therefore act as potential biomarkers for dementia due to Alzheimer’s disease. This review is aimed at highlighting evidences that support blood plasma electrical properties, e.g., dielectric constant and conductivity as possible novel biomarkers for the early development and progression of dementia due to Alzheimer’s disease.

scholarly journals Induced Pluripotent Stem Cell-Derived Neural Precursors Improve Memory, Synaptic and Pathological Abnormalities in a Mouse Model of Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1802
Author(s):  
Enrique Armijo ◽  
George Edwards ◽  
Andrea Flores ◽  
Jorge Vera ◽  
Mohammad Shahnawaz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Memory Loss ◽  
Amyloid Β ◽  
Cerebral Atrophy ◽  
Brain Inflammation ◽  
Neural Precursors ◽  
Model Of Alzheimer’S Disease ◽  
Induced Pluripotent

Alzheimer’s disease (AD) is the most common type of dementia in the elderly population. The disease is characterized by progressive memory loss, cerebral atrophy, extensive neuronal loss, synaptic alterations, brain inflammation, extracellular accumulation of amyloid-β (Aβ) plaques, and intracellular accumulation of hyper-phosphorylated tau (p-tau) protein. Many recent clinical trials have failed to show therapeutic benefit, likely because at the time in which patients exhibit clinical symptoms the brain is irreversibly damaged. In recent years, induced pluripotent stem cells (iPSCs) have been suggested as a promising cell therapy to recover brain functionality in neurodegenerative diseases such as AD. To evaluate the potential benefits of iPSCs on AD progression, we stereotaxically injected mouse iPSC-derived neural precursors (iPSC-NPCs) into the hippocampus of aged triple transgenic (3xTg-AD) mice harboring extensive pathological abnormalities typical of AD. Interestingly, iPSC-NPCs transplanted mice showed improved memory, synaptic plasticity, and reduced AD brain pathology, including a reduction of amyloid and tangles deposits. Our findings suggest that iPSC-NPCs might be a useful therapy that could produce benefit at the advanced clinical and pathological stages of AD.

scholarly journals Improved Bioavailability of Montelukast through a Novel Oral Mucoadhesive Film in Humans and Mice

Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 12
Author(s):  
Johanna Michael ◽  
Diana Bessa de Sousa ◽  
Justin Conway ◽  
Erick Gonzalez-Labrada ◽  
Rodolphe Obeid ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Neurodegenerative Diseases ◽  
Significant Proportion ◽  
Preclinical Model ◽  
Dependent Manner ◽  
Promising Alternative ◽  
Model Of Alzheimer’S Disease ◽  
Acute And Chronic Exposure

The leukotriene receptor antagonist Montelukast (MTK) is an approved medication for the treatment of asthma and allergic rhinitis. The existing marketed tablet forms of MTK exhibit inconsistent uptake and bioavailability, which partially explains the presence of a significant proportion of MTK low- and non-responders in the population. Besides that, tablets are suboptimal formulations for patients suffering from dysphagia, for example, seen in patients with neurodegenerative diseases such as Alzheimer’s disease, a disease with increasing interest in repurposing of MTK. This, and the need for an improved bioavailability, triggered us to reformulate MTK. Our aim was to develop a mucoadhesive MTK film with good safety and improved pharmacological features, i.e., an improved bioavailability profile in humans as well as in a mouse model of Alzheimer’s disease. We tested dissolution of the MTK mucoadhesive film and assessed pharmacoexposure and kinetics after acute and chronic oral application in mice. Furthermore, we performed a Phase I analysis in humans, which included a comparison with the marketed tablet form as well as a quantitative analysis of the MTK levels in the cerebrospinal fluid. The novel MTK film demonstrated significantly improved bioavailability compared to the marketed tablet in the clinical Phase 1a study. Furthermore, there were measurable amounts of MTK present in the cerebrospinal fluid (CSF). In mice, MTK was detected in serum and CSF after acute and chronic exposure in a dose-dependent manner. The mucoadhesive film of MTK represents a promising alternative for the tablet delivery. The oral film might lower the non-responder rate in patients with asthma and might be an interesting product for repurposing of MTK in other diseases. As we demonstrate Blood-Brain-Barrier (BBB) penetrance in a preclinical model, as well as in a clinical study, the oral film of MTK might find its use as a therapeutic for acute and chronic neurodegenerative diseases such as dementias and stroke.

scholarly journals Coffee polyphenols prevent cognitive dysfunction and suppress amyloid β plaques in APP/PS2 transgenic mouse

2018 ◽  
Author(s):  
Keiko Ishida ◽  
Masaki Yamamoto ◽  
Koichi Misawa ◽  
Noriyasu Ota ◽  
Akira Shimotoyodome
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mouse ◽  
Cognitive Dysfunction ◽  
Amyloid Β ◽  
Morris Water Maze Test ◽  
Dependent Manner ◽  
Chlorogenic Acids ◽  
Caffeoylquinic Acid ◽  
Model Of Alzheimer’S Disease

AbstractEpidemiological studies have found that habitual coffee consumption may reduce the risk of Alzheimer’s disease. Coffee contains numerous phenolic compounds (coffee polyphenols) such as chlorogenic acids. However, evidence demonstrating the contribution of chlorogenic acids in preventing cognitive dysfunction induced by Alzheimer’s disease is limited. In this study, we investigated the effect of chlorogenic acids on prevention of cognitive dysfunction in APP/PS2 transgenic mouse model of Alzheimer’s disease. Five-week-old APP/PS2 mice were administered a diet supplemented with coffee polyphenols daily for 5 months. The memory and cognitive function of mice was determined using the novel object recognition test, the Morris water maze test, and the step-through passive avoidance test. We found that chronic treatment with coffee polyphenols prevented cognitive dysfunction and significantly reduced hippocampal Aβ deposition. We then determined the effect of 5-caffeoylquinic acid, one of the primary components of coffee polyphenols, on Aβ formation. 5-Caffeoylquinic acid did not inhibit Aβ fibrillation, but degraded Aβ fibrils in a dose-dependent manner. In conclusion, these results demonstrate that coffee polyphenols prevented cognitive deficits and alleviated Aβ plaque deposition via disaggregation of Aβ in APP/PS2 mouse.

scholarly journals Development of Random Forest Algorithm Based Prediction Model of Alzheimer’s Disease Using Neurodegeneration Pattern

2021 ◽  
Vol 18 (1) ◽  
pp. 69-79
Author(s):  
JeeYoung Kim ◽  
Minho Lee ◽  
Min Kyoung Lee ◽  
Sheng-Min Wang ◽  
Nak-Young Kim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Random Forest ◽  
Diagnostic Accuracy ◽  
Prediction Model ◽  
Clinical Symptoms ◽  
The Elderly ◽  
Structural Mri ◽  
Brain Segmentation ◽  
Model Of Alzheimer’S Disease

Objective Alzheimer’s disease (AD) is the most common type of dementia and the prevalence rapidly increased as the elderly population increased worldwide. In the contemporary model of AD, it is regarded as a disease continuum involving preclinical stage to severe dementia. For accurate diagnosis and disease monitoring, objective index reflecting structural change of brain is needed to correctly assess a patient’s severity of neurodegeneration independent from the patient’s clinical symptoms. The main aim of this paper is to develop a random forest (RF) algorithm-based prediction model of AD using structural magnetic resonance imaging (MRI).Methods We evaluated diagnostic accuracy and performance of our RF based prediction model using newly developed brain segmentation method compared with the Freesurfer’s which is a commonly used segmentation software.Results Our RF model showed high diagnostic accuracy for differentiating healthy controls from AD and mild cognitive impairment (MCI) using structural MRI, patient characteristics, and cognitive function (HC vs. AD 93.5%, AUC 0.99; HC vs. MCI 80.8%, AUC 0.88). Moreover, segmentation processing time of our algorithm (<5 minutes) was much shorter than of Freesurfer’s (6–8 hours).Conclusion Our RF model might be an effective automatic brain segmentation tool which can be easily applied in real clinical practice.

Biomarkers in Alzheimer’s disease

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Manuel H. Janeiro ◽  
Carlos G. Ardanaz ◽  
Noemí Sola-Sevilla ◽  
Jinya Dong ◽  
María Cortés-Erice ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Biological Fluids ◽  
Pathological Process ◽  
Positron Emission ◽  
Cerebrospinal Fluid Biomarkers ◽  
Novel Biomarkers ◽  
Definition Of ◽  
T Tau

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disease. AD is the main cause of dementia worldwide and aging is the main risk factor for developing the illness. AD classical diagnostic criteria rely on clinical data. However, the development of a biological definition of AD using biomarkers that reflect the underling neuropathology is needed.ContentThe aim of this review is to describe the main outcomes when measuring classical and novel biomarkers in biological fluids or neuroimaging.SummaryNowadays, there are three classical biomarkers for the diagnosis of AD: Aβ42, t-Tau and p-Tau. The diagnostic use of cerebrospinal fluid biomarkers is limited due to invasive collection by lumbar puncture with potential side effects. Plasma/serum measurements are the gold standard in clinics, because they are minimally invasive and, in consequence, easily collected and processed. The two main proteins implicated in the pathological process, Aβ and Tau, can be visualized using neuroimaging techniques, such as positron emission tomography.OutlookAs it is currently accepted that AD starts decades before clinical symptoms could be diagnosed, the opportunity to detect biological alterations prior to clinical symptoms would allow early diagnosis or even perhaps change treatment possibilities.

scholarly journals Microarray Profile of Long Noncoding RNA and Messenger RNA Expression in a Model of Alzheimer’s Disease

Life ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 64
Author(s):  
Linlin Wang ◽  
Li Zeng ◽  
Hailun Jiang ◽  
Zhuorong Li ◽  
Rui Liu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Skills ◽  
Messenger Rna ◽  
Noncoding Rna ◽  
Model Of Alzheimer’S Disease ◽  
Conserved Genes ◽  
Novel Biomarkers ◽  
The Brain ◽  
Ad Mouse Model

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by a deficiency in cognitive skills. Although long noncoding RNAs (lncRNAs) have been proposed as associated with AD, the aberrant lncRNAs expression and the co-expression of lncRNAs-mRNAs network in AD remains unclear. Therefore, in this study, lncRNA microarray was performed on the brain of APP/PS1 mice at different age, widely used as an AD mouse model, and on age-matched wide-type controls. Our results identified a total of 3306 lncRNAs and 2458 mRNAs as aberrantly expressed among AD mice at different age and their age-matched control. Gene Ontology and pathway analysis of the AD-related lncRNAs and mRNAs indicated that neuroinflammation-related and synaptic transmission signaling pathways represented the main enriched pathways. An lncRNA–mRNA–miRNA network between the differentially expressed transcripts was constructed. Moreover, an mRNA–miRNA network between both significantly dysregulated and highly conserved genes was also constructed, and among this network, the IGF1, P2RX7, TSPO, SERPINE1, EGFR, HMOX1, and NFE212 genes were predicted to play a role in the development of AD. In conclusion, this study illustrated the prognostic value of lncRNAs and mRNAs associated to AD pathology by microarray analysis and might provide potential novel biomarkers in the diagnosis and treatment of AD.

γ-Hydroxybutyrate (Xyrem) ameliorates clinical symptoms and neuropathology in a mouse model of Alzheimer's disease

2015 ◽  
Vol 36 (2) ◽  
pp. 832-844 ◽  
Author(s):  
Christian Klein ◽  
Chantal Mathis ◽  
Géraldine Leva ◽  
Christine Patte-Mensah ◽  
Jean-Christophe Cassel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Clinical Symptoms ◽  
Model Of Alzheimer’S Disease

scholarly journals Improved bioavailability of montelukast through a novel oral mucoadhesive film in humans and mice

2020 ◽  
Author(s):  
Johanna Michael ◽  
Diana Bessa de Sousa ◽  
Justin Conway ◽  
Erick Gonzales-Labrada ◽  
Rodolphe Obeid ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Neurodegenerative Diseases ◽  
Significant Proportion ◽  
Pharmacokinetic Analysis ◽  
Dependent Manner ◽  
Promising Alternative ◽  
Model Of Alzheimer’S Disease ◽  
Acute And Chronic Exposure

AbstractThe leukotriene receptor antagonist Montelukast (MTK) is an approved medication for the treatment of asthma and allergic rhinitis. The existing marketed tablet forms of MTK exhibit inconsistent uptake and bioavailability, which partially explains the presence of a significant proportion of MTK low- and non-responders in the population. Besides that, tablets are suboptimal formulations for patients suffering of dysphagia, for example seen in COVID-19 patients or in patients with neurodegenerative diseases such as Alzheimer’s Disease. The increasing interest in repurposing of MTK for the treatment of such patients and the need for an improved bioavailability triggered us to reformulate MTK. The aim was to develop a mucoadhesive MTK film with a good safety and improved pharmacological, i.e. improved bioavailability, profile in humans as well as in a mouse model of Alzheimer’s Disease.We tested dissolution of the mucoadhesive film containing MTK in saliva buffer and assessed pharmacoexposure and −kinetics after acute and chronic oral application in mice. Furthermore, we performed a Phase I safety / bioavailability / pharmacokinetic analysis in healthy volunteers. The latter included a comparison with the marketed tablet form as well as a quantitative analysis of the MTK levels in the cerebrospinal fluid.The novel MTK film demonstrated significantly improved bioavailability compared to the marketed tablet in the clinical phase 1a study in healthy humans. Furthermore, there were measurable amounts of MTK present in the cerebrospinal fluid (CSF) at the 3.0 and 7.0 hour time points post drug administration in humans. In mice, MTK was detected in serum and CSF after acute and chronic exposure in a dose-dependent manner.The developed mucoadhesive film of MTK represents a promising alternative for the tablet delivery. The oral film might lower the non-responder rate in patients with asthma and might be an interesting product for repurposing of MTK in other diseases. As we demonstrate BBB penetrance in a preclinical model as well as in a clinical study, the oral film of MTK might find its use as a therapeutic for acute and chronic neurodegenerative diseases such as dementias and stroke.

scholarly journals Impaired Spatial Reorientation in the 3xTg-AD Mouse Model of Alzheimer’s Disease

2018 ◽  
Author(s):  
Alina C. Stimmell ◽  
David Baglietto-Vargas ◽  
Shawn C. Moseley ◽  
Valérie Lapointe ◽  
Lauren M. Thompson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Dorsal Hippocampus ◽  
Brain Stimulation Reward ◽  
Spatial Disorientation ◽  
Model Of Alzheimer’S Disease ◽  
Spatial Reorientation ◽  
Getting Lost ◽  
To Receive

AbstractIn early Alzheimer’s disease (AD) spatial navigation is impaired; however, the precise cause of this impairment is unclear. Recent evidence suggests that getting lost in new surroundings is one of the first impairments to emerge in AD. It is possible that getting lost in new surroundings represents a failure to use distal cues to get oriented in space. Therefore, we set out to look for impaired use of distal cues for spatial orientation in a mouse model of amyloidosis (3xTg-AD). To do this, we trained mice to shuttle to the end of a track and back to an enclosed start box to receive a water reward. Then, mice were trained to stop in an unmarked reward zone to receive a brain stimulation reward. The time required to remain in the zone for a reward was increased across training, and the track was positioned in a random start location for each trial. We found that 6-month female, but not male, 3xTg-AD mice were impaired. Male and female mice had only intracellular pathology and male mice had less pathology, particularly in the dorsal hippocampus. Thus, AD may cause spatial disorientation as a result of impaired use of landmarks.

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