Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2858

Search results for: alzheimer’s disease

2858 Alzheimer’s Disease Measured in Work Organizations

Authors: Katherine Denise Queri

Abstract:

The effects of sick workers have an impact in administration of labor. This study aims to provide knowledge on the disease that is Alzheimer’s while presenting an answer to the research question of when and how is the disease considered as a disaster inside the workplace. The study has the following as its research objectives: 1. Define Alzheimer’s disease, 2. Evaluate the effects and consequences of an employee suffering from Alzheimer’s disease, 3. Determine the concept of organizational effectiveness in the area of Human Resources, and 4. Identify common figures associated with Alzheimer’s disease. The researcher gathered important data from books, video presentations, and interviews of workers suffering from Alzheimer’s disease and from the internet. After using all the relevant data collection instruments mentioned, the following data emerged: 1. Alzheimer’s disease has certain consequences inside the workplace, 2. The occurrence of Alzheimer’s Disease in an employee’s life greatly affects the company where the worker is employed, and 3. The concept of workplace efficiency suggests that an employer must prepare for such disasters that Alzheimer’s disease may bring to the company where one is employed. Alzheimer’s disease can present disaster in any workplace.

Keywords: administration, Alzheimer's disease, conflict, disaster, employment

Procedia PDF Downloads 357
2857 Synthesis of Metal Curcumin Complexes with Iron(III) and Manganese(II): The Effects on Alzheimer's Disease

Authors: Emel Yildiz, Nurcan Biçer, Fazilet Aksu, Arash Alizadeh Yegani

Abstract:

Plants provide the wealth of bioactive compounds, which exert a substantial strategy for the treatment of neurological disorders such as Alzheimer's disease. Recently, a lot of studies have explored the medicinal properties of curcumin, including antitumoral, antimicrobial, anti-inflammatory, antioxidant, antiviral, and anti-Alzheimer's disease effects. Metal complexes of curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) were synthesized with Mn(II) and Fe(III). The structures of synthesized metal complexes have been characterized by using spectroscopic and analytic methods such as elemental analysis, magnetic susceptibility, FT-IR, AAS, TG and argentometric titration. It was determined that the complexes have octahedral geometry. The effects of the metal complexes on the disorder of memory, which is an important symptom of Alzheimer's Disease were studied on lab rats with Plus-Maze Tests at Behavioral Pharmacology Laboratory.

Keywords: curcumin, Mn(II), Fe(III), Alzheimer disease, beta amyloid 25-35

Procedia PDF Downloads 207
2856 3 Dimensional (3D) Assesment of Hippocampus in Alzheimer’s Disease

Authors: Mehmet Bulent Ozdemir, Sultan Çagirici, Sahika Pinar Akyer, Fikri Turk

Abstract:

Neuroanatomical appearance can be correlated with clinical or other characteristics of illness. With the introduction of diagnostic imaging machines, producing 3D images of anatomic structures, calculating the correlation between subjects and pattern of the structures have become possible. The aim of this study is to examine the 3D structure of hippocampus in cases with Alzheimer disease in different dementia severity. For this purpose, 62 female and 38 male- 68 patients’s (age range between 52 and 88) MR scanning were imported to the computer. 3D model of each right and left hippocampus were developed by a computer aided propramme-Surf Driver 3.5. Every reconstruction was taken by the same investigator. There were different apperance of hippocampus from normal to abnormal. In conclusion, These results might improve the understanding of the correlation between the morphological changes in hippocampus and clinical staging in Alzheimer disease.

Keywords: Alzheimer disease, hippocampus, computer-assisted anatomy, 3D

Procedia PDF Downloads 387
2855 Neural Network Based Decision Trees Using Machine Learning for Alzheimer's Diagnosis

Authors: P. S. Jagadeesh Kumar, Tracy Lin Huan, S. Meenakshi Sundaram

Abstract:

Alzheimer’s disease is one of the prevalent kind of ailment, expected for impudent reconciliation or an effectual therapy is to be accredited hitherto. Probable detonation of patients in the upcoming years, and consequently an enormous deal of apprehension in early discovery of the disorder, this will conceivably chaperon to enhanced healing outcomes. Complex impetuosity of the brain is an observant symbolic of the disease and a unique recognition of genetic sign of the disease. Machine learning alongside deep learning and decision tree reinforces the aptitude to absorb characteristics from multi-dimensional data’s and thus simplifies automatic classification of Alzheimer’s disease. Susceptible testing was prophesied and realized in training the prospect of Alzheimer’s disease classification built on machine learning advances. It was shrewd that the decision trees trained with deep neural network fashioned the excellent results parallel to related pattern classification.

Keywords: Alzheimer's diagnosis, decision trees, deep neural network, machine learning, pattern classification

Procedia PDF Downloads 206
2854 Reminiscence Therapy for Alzheimer’s Disease Restrained on Logistic Regression Based Linear Bootstrap Aggregating

Authors: P. S. Jagadeesh Kumar, Mingmin Pan, Xianpei Li, Yanmin Yuan, Tracy Lin Huan

Abstract:

Researchers are doing enchanting research into the inherited features of Alzheimer’s disease and probable consistent therapies. In Alzheimer’s, memories are extinct in reverse order; memories formed lately are more transitory than those from formerly. Reminiscence therapy includes the conversation of past actions, trials and knowledges with another individual or set of people, frequently with the help of perceptible reminders such as photos, household and other acquainted matters from the past, music and collection of tapes. In this manuscript, the competence of reminiscence therapy for Alzheimer’s disease is measured using logistic regression based linear bootstrap aggregating. Logistic regression is used to envisage the experiential features of the patient’s memory through various therapies. Linear bootstrap aggregating shows better stability and accuracy of reminiscence therapy used in statistical classification and regression of memories related to validation therapy, supportive psychotherapy, sensory integration and simulated presence therapy.

Keywords: Alzheimer’s disease, linear bootstrap aggregating, logistic regression, reminiscence therapy

Procedia PDF Downloads 209
2853 Trigonelline: A Promising Compound for The Treatment of Alzheimer's Disease

Authors: Mai M. Farid, Ximeng Yang, Tomoharu Kuboyama, Chihiro Tohda

Abstract:

Trigonelline is a major alkaloid component derived from Trigonella foenum-graecum L. (fenugreek) and has been reported before as a potential neuroprotective agent, especially in Alzheimer’s disease (AD). However, the previous data were unclear and used model mice were not well established. In the present study, the effect of trigonelline on memory function was investigated in Alzheimer’s disease transgenic model mouse, 5XFAD which overexpresses the mutated APP and PS1 genes. Oral administration of trigonelline for 14 days significantly enhanced object recognition and object location memories. Plasma and cerebral cortex were isolated at 30 min, 1h, 3h, and 6 h after oral administration of trigonelline. LC-MS/MS analysis indicated that trigonelline was detected in both plasma and cortex from 30 min after, suggesting good penetration of trigonelline into the brain. In addition, trigonelline significantly ameliorated axonal and dendrite atrophy in Amyloid β-treated cortical neurons. These results suggest that trigonelline could be a promising therapeutic candidate for AD.

Keywords: alzheimer’s disease, cortical neurons, LC-MS/MS analysis, trigonelline

Procedia PDF Downloads 70
2852 Predicting the Diagnosis of Alzheimer’s Disease: Development and Validation of Machine Learning Models

Authors: Jay L. Fu

Abstract:

Patients with Alzheimer's disease progressively lose their memory and thinking skills and, eventually, the ability to carry out simple daily tasks. The disease is irreversible, but early detection and treatment can slow down the disease progression. In this research, publicly available MRI data and demographic data from 373 MRI imaging sessions were utilized to build models to predict dementia. Various machine learning models, including logistic regression, k-nearest neighbor, support vector machine, random forest, and neural network, were developed. Data were divided into training and testing sets, where training sets were used to build the predictive model, and testing sets were used to assess the accuracy of prediction. Key risk factors were identified, and various models were compared to come forward with the best prediction model. Among these models, the random forest model appeared to be the best model with an accuracy of 90.34%. MMSE, nWBV, and gender were the three most important contributing factors to the detection of Alzheimer’s. Among all the models used, the percent in which at least 4 of the 5 models shared the same diagnosis for a testing input was 90.42%. These machine learning models allow early detection of Alzheimer’s with good accuracy, which ultimately leads to early treatment of these patients.

Keywords: Alzheimer's disease, clinical diagnosis, magnetic resonance imaging, machine learning prediction

Procedia PDF Downloads 62
2851 DNAJB6 Chaperone Prevents the Aggregation of Intracellular but not Extracellular Aβ Peptides Associated with Alzheimer’s Disease

Authors: Rasha M. Hussein, Reem M. Hashem, Laila A. Rashed

Abstract:

Alzheimer’s disease is the most common dementia disease in the elderly. It is characterized by the accumulation of extracellular amyloid β (Aβ) peptides and intracellular hyper-phosphorylated tau protein. In addition, recent evidence indicates that accumulation of intracellular amyloid β peptides may play a role in Alzheimer’s disease pathogenesis. This suggests that intracellular Heat Shock Proteins (HSP) that maintain the protein quality control in the cell might be potential candidates for disease amelioration. DNAJB6, a member of DNAJ family of HSP, effectively prevented the aggregation of poly glutamines stretches associated with Huntington’s disease both in vitro and in cells. In addition, DNAJB6 was found recently to delay the aggregation of Aβ42 peptides in vitro. In the present study, we investigated the ability of DNAJB6 to prevent the aggregation of both intracellular and extracellular Aβ peptides using transfection of HEK293 cells with Aβ-GFP and recombinant Aβ42 peptides respectively. We performed western blotting and immunofluorescence techniques. We found that DNAJB6 can prevent Aβ-GFP aggregation, but not the seeded aggregation initiated by extracellular Aβ peptides. Moreover, DNAJB6 required interaction with HSP70 to prevent the aggregation of Aβ-GFP protein and its J-domain was essential for this anti-aggregation activity. Interestingly, overexpression of other DNAJ proteins as well as HSPB1 suppressed Aβ-GFP aggregation efficiently. Our findings suggest that DNAJB6 is a promising candidate for the inhibition of Aβ-GFP mediated aggregation through a canonical HSP70 dependent mechanism.

Keywords: , Alzheimer’s disease, chaperone, DNAJB6, aggregation

Procedia PDF Downloads 434
2850 Trigonella foenum-graecum Seeds Extract as Therapeutic Candidate for Treatment of Alzheimer's Disease

Authors: Mai M. Farid, Ximeng Yang, Tomoharu Kuboyama, Yuna Inada, Chihiro Tohda

Abstract:

Intro: Trigonella foenum-graecum (Fenugreek), from Fabaceae family is a well-known plant traditionally used as food and medicine. Many pharmacological effects of Trigonella foenum- graecum seeds extract (TF extract) were evaluated such as anti-diabetic, anti-tumor and anti-dementia effects using in vivo models. Regarding the anti-dementia effects of TF extract, diabetic rats, aluminum chloride-induced amnesia rats and scopolamine-injected mice were used previously for evaluation, which are not well established as Alzheimer’s disease models. In addition, those previous studies, active constituents in TF extract for memory function were not identified. Method: This study aimed to clarify the effect of TF extract on Alzheimer’s disease model, 5XFAD mouse that overexpresses mutated APP and PS1 genes and determine the major active constituent in the brain after oral intake of TF extract. Results: Trigonelline was detected in the cerebral cortex of 5XFAD mice after 24 hours of oral administration of TF extract by LC-MS/MS. Oral administration of TF extract for 17 days improved object location memory in 5XFAD mice. Conclusion: These results suggest that TF extract and its active constituents could be an expected therapeutic candidate for Alzheimer’s disease.

Keywords: Alzheimer's disease, LC-MS/MS, memory recovery, Trigonella foenum-graecum Seeds, 5XFAD mice

Procedia PDF Downloads 60
2849 Combined Use of FMRI and Voxel-Based Morphometry in Assessment of Memory Impairment in Alzheimer's Disease Patients

Authors: A. V. Sokolov, S. V. Vorobyev, A. Yu. Efimtcev, V. Yu. Lobzin, I. A. Lupanov, O. A. Cherdakov, V. A. Fokin

Abstract:

Alzheimer’s disease (AD) is the most common form of dementia. Different brain regions are involved to the pathological process of AD. The purpose of this study was to evaluate brain activation by visual memory task in patients with Alzheimer's disease and determine correlation between memory impairment and atrophy of memory specific brain regions of frontal and medial temporal lobes. To investigate the organization of memory and localize cortical areas activated by visual memory task we used functional magnetic resonance imaging and to evaluate brain atrophy of patients with Alzheimer's disease we used voxel-based morphometry. FMRI was performed on 1.5 T MR-scanner Siemens Magnetom Symphony with BOLD (Blood Oxygenation Level Dependent) technique, based on distinctions of magnetic properties of hemoglobin. For test stimuli we used series of 12 not related images for "Baseline" and 12 images with 6 presented before for "Active". Stimuli were presented 3 times with reduction of repeated images to 4 and 2. Patients with Alzheimer's disease showed less activation in hippocampal formation (HF) region and parahippocampal gyrus then healthy persons of control group (p<0.05). The study also showed reduced activation in posterior cingulate cortex (p<0.001). Voxel-based morphometry showed significant atrophy of grey matter in Alzheimer’s disease patients, especially of both temporal lobes (fusiform and parahippocampal gyri); frontal lobes (posterior cingulate and superior frontal gyri). The study showed correlation between memory impairment and atrophy of memory specific brain regions of frontal and medial temporal lobes. Thus, reduced activation in hippocampal formation and parahippocampal gyri, in posterior cingulate gyrus in patients with Alzheimer's disease correlates to significant atrophy of these regions, detected by voxel-based morphometry, and to deterioration of specific cognitive functions.

Keywords: Alzheimer’s disease, functional MRI, voxel-based morphometry

Procedia PDF Downloads 238
2848 Diagnosis of Alzheimer Diseases in Early Step Using Support Vector Machine (SVM)

Authors: Amira Ben Rabeh, Faouzi Benzarti, Hamid Amiri, Mouna Bouaziz

Abstract:

Alzheimer is a disease that affects the brain. It causes degeneration of nerve cells (neurons) and in particular cells involved in memory and intellectual functions. Early diagnosis of Alzheimer Diseases (AD) raises ethical questions, since there is, at present, no cure to offer to patients and medicines from therapeutic trials appear to slow the progression of the disease as moderate, accompanying side effects sometimes severe. In this context, analysis of medical images became, for clinical applications, an essential tool because it provides effective assistance both at diagnosis therapeutic follow-up. Computer Assisted Diagnostic systems (CAD) is one of the possible solutions to efficiently manage these images. In our work; we proposed an application to detect Alzheimer’s diseases. For detecting the disease in early stage we used the three sections: frontal to extract the Hippocampus (H), Sagittal to analysis the Corpus Callosum (CC) and axial to work with the variation features of the Cortex(C). Our method of classification is based on Support Vector Machine (SVM). The proposed system yields a 90.66% accuracy in the early diagnosis of the AD.

Keywords: Alzheimer Diseases (AD), Computer Assisted Diagnostic(CAD), hippocampus, Corpus Callosum (CC), cortex, Support Vector Machine (SVM)

Procedia PDF Downloads 267
2847 Nanoparticles in Drug Delivery and Therapy of Alzeheimer's Disease

Authors: Nirupama Dixit, Anyaa Mittal, Neeru Sood

Abstract:

Alzheimer’s disease (AD) is a progressive form of dementia, contributing to up to 70% of cases, mostly observed in elderly but is not restricted to old age. The pathophysiology of the disease is characterized by specific pathological changes in brain. The changes (i.e. accumulation of metal ions in brain, formation of extracellular β-amyloid (Aβ) peptide aggregates and tangle of hyper phosphorylated Tau protein inside neurons) damage the neuronal connections irreversibly. The current issues in improvement of life quality of Alzheimer's patient lies in the fact that the diagnosis is made at a late stage of the disease and the medications do not treat the basic causes of Alzheimer's. The targeted delivery of drug through the blood brain barrier (BBB) poses several limitations via traditional approaches for treatment. To overcome these drug delivery limitation, nanoparticles provide a promising solution. This review focuses on current strategies for efficient targeted drug delivery using nanoparticles and improving the quality of therapy provided to the patient. Nanoparticles can be used to encapsulate drug (which is generally hydrophobic) to ensure its passage to brain; they can be conjugated to metal ion chelators to reduce the metal load in neural tissue thus lowering the harmful effects of oxidative damage; can be conjugated with drug and monoclonal antibodies against BBB endogenous receptors. Finally this review covers how the nanoparticles can play a role in diagnosing the disease.

Keywords: Alzheimer's disease, β-amyloid plaques, blood brain barrier, metal chelators, nanoparticles

Procedia PDF Downloads 411
2846 Early Diagnosis of Alzheimer's Disease Using a Combination of Images Processing and Brain Signals

Authors: E. Irankhah, M. Zarif, E. Mazrooei Rad, K. Ghandehari

Abstract:

Alzheimer's prevalence is on the rise, and the disease comes with problems like cessation of treatment, high cost of treatment, and the lack of early detection methods. The pathology of this disease causes the formation of protein deposits in the brain of patients called plaque amyloid. Generally, the diagnosis of this disease is done by performing tests such as a cerebrospinal fluid, CT scan, MRI, and spinal cord fluid testing, or mental testing tests and eye tracing tests. In this paper, we tried to use the Medial Temporal Atrophy (MTA) method and the Leave One Out (LOO) cycle to extract the statistical properties of the three Fz, Pz, and Cz channels of ERP signals for early diagnosis of this disease. In the process of CT scan images, the accuracy of the results is 81% for the healthy person and 88% for the severe patient. After the process of ERP signaling, the accuracy of the results for a healthy person in the delta band in the Cz channel is 81% and in the alpha band the Pz channel is 90%. In the results obtained from the signal processing, the results of the severe patient in the delta band of the Cz channel were 89% and in the alpha band Pz channel 92%.

Keywords: Alzheimer's disease, image and signal processing, LOO cycle, medial temporal atrophy

Procedia PDF Downloads 122
2845 Expression of ACSS2 Genes in Peripheral Blood Mononuclear Cells of Patients with Alzheimer’s Disease

Authors: Ali Bayram, Burak Uz, Remzi Yiğiter

Abstract:

The impairment of lipid metabolism in the central nervous system has been suggested as a critical factor of Alzheimer’s disease (AD) pathogenesis. Homo sapiens acyl-coenyme A synthetase short-chain family member 2 (ACSS2) gene encodes the enzyme acetyl-Coenzyme A synthetase (AMP forming; AceCS) providing acetyl-coenzyme A (Ac-CoA) for various physiological processes, such as cholesterol and fatty acid synthesis, as well as the citric acid cycle. We investigated ACSS2, transcript variant 1 (ACSS2*1), mRNA levels in the peripheral blood mononuclear cells (PBMC) of patients with AD and compared them with the controls. The study group comprised 50 patients with the diagnosis of AD who have applied to Gaziantep University Faculty of Medicine, and Department of Neurology. 49 healthy individuals without any neurodegenerative disease are included as controls. ACSS2 mRNA expression in PBMC of AD/control patients was 0.495 (95% confidence interval: 0.410-0.598), p= .000000001902). Further studies are needed to better clarify this association.

Keywords: Alzheimer’s disease, ACSS2 Genes, mRNA expression, RT-PCR

Procedia PDF Downloads 291
2844 Calculating Ventricle’s Area Based on Clinical Dementia Rating Values on Coronal MRI Image

Authors: Retno Supriyanti, Ays Rahmadian Subhi, Yogi Ramadhani, Haris B. Widodo

Abstract:

Alzheimer is one type of disease in the elderly that may occur in the world. The severity of the Alzheimer can be measured using a scale called Clinical Dementia Rating (CDR) based on a doctor's diagnosis of the patient's condition. Currently, diagnosis of Alzheimer often uses MRI machine, to know the condition of part of the brain called Hippocampus and Ventricle. MRI image itself consists of 3 slices, namely Coronal, Sagittal and Axial. In this paper, we discussed the measurement of the area of the ventricle especially in the Coronal slice based on the severity level referring to the CDR value. We use Active Contour method to segment the ventricle’s region, therefore that ventricle’s area can be calculated automatically. The results show that this method can be used for further development in the automatic diagnosis of Alzheimer.

Keywords: Alzheimer, CDR, coronal, ventricle, active contour

Procedia PDF Downloads 185
2843 Neuroprotective Effects of Dehydroepiandrosterone (DHEA) in Rat Model of Alzheimer’s Disease

Authors: Hanan F. Aly, Fateheya M. Metwally, Hanaa H. Ahmed

Abstract:

The current study is undertaken to elucidate a possible neuroprotective role of dehydroepiandrosterone (DHEA) against the development of Alzheimer’s disease in experimental rat model. Alzheimer’s disease was produced in young female ovariectomized rats by intraperitoneal administration of AlCl3 (4.2 mg/kg body weight) daily for 12 weeks. Half of these animals also received orally DHEA (250 mg/kg body weight, three times weekly) for 18 weeks. Control groups of animals received either DHAE alone, or no DHEA, or were not ovariectomized. After such treatment the animals were analyzed for oxidative stress biomarkers such as hydrogen peroxide, nitric oxide and malondialdehyde, total antioxidant capacity, reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase activities, antiapoptotic marker Bcl-2 and brain derived neurotrophic factor. Also, brain cholinergic markers (acetylcholinesterase and acetylcholine) were determined. The results revealed significant increase in oxidative stress parameters associated with significant decrease in the antioxidant enzyme activities in Al-intoxicated ovariectomized rats. Significant depletion in brain Bcl-2 and brain-derived neurotrophic factor levels were also detected. Moreover, significant elevations in brain acetylcholinesterase activity accompanied with significant reduction in acetylcholine level were recorded. Significant amelioration in all investigated parameters was detected as a result of treatment of Al-intoxicated ovariectomized rats with DHEA. These results were confirmed by histological examination of brain sections. These results clearly indicate a neuroprotective effect of DHEA against Alzheimer’s disease.

Keywords: Alzheimer’s disease, oxidative stress, apoptosis, dehydroepiandrosterone

Procedia PDF Downloads 242
2842 The Role of Inflammasomes for aβ Microglia Phagocytosis in Alzheimer Disease

Authors: Francesca La Rosa , Marina Saresella, Mario Clerici, Michael Heneka

Abstract:

Neuroinflammation plays a key role in the modulation of the pathogenesis of neurodegenerative disorder such as Alzheimer's Disease (AD). Microglia, the main immune effector of the brain, are able to migrate to sites of Amyloid-beta (Aβ) deposition to eliminate Aβ phagocytosis upon activation by multiple receptors: Toll like receptors and scavenger receptors. The issue of whether microglia are able to eliminate pathological lesions such as neurofibrillary tangles or senile plaques from AD brain still remains the matter of controversy. Recent data suggest that the Nod Like Receptor 3 (NLRP3), multiprotein inflammasome complexes, plays a role in AD, as its activation in the microglia by Aβ triggers. IL-1β is produced as a biologically inactive pro-form and requires caspase-1 for activation and secretion. Caspase-1 activity is controlled by inflammasomes. We investigate about the importance of inflammasomes complex in the Aβ phagocytosis and its degradation. The preliminary results of phagocytosis assay and immunofluorescent experiment on primary Microglia cells to lipopolysaccharide (LPS) an Aβ exposure show that a previous treatment with LPS reduce Aβ phagocytosis. Different results were obtained in Primary Microglia wild type, NLRP3 and ASC Knockout suggesting a real inflammasomes involvement in Alzheimer's pathology. Inflammasomes inactivation reduces the production of inflammatory cytokines prolonging the protective activity of microglia and Aβ clearance, featuring a typical microglia phenotype of the early stage of AD disease.

Keywords: Alzheimer disease, innate immunity, neuroinflammation, NLRP3

Procedia PDF Downloads 346
2841 Language Processing of Seniors with Alzheimer’s Disease: From the Perspective of Temporal Parameters

Authors: Lai Yi-Hsiu

Abstract:

The present paper aims to examine the language processing of Chinese-speaking seniors with Alzheimer’s disease (AD) from the perspective of temporal cues. Twenty healthy adults, 17 healthy seniors, and 13 seniors with AD in Taiwan participated in this study to tell stories based on two sets of pictures. Nine temporal cues were fetched and analyzed. Oral productions in Mandarin Chinese were compared and discussed to examine to what extent and in what way these three groups of participants performed with significant differences. Results indicated that the age effects were significant in filled pauses. The dementia effects were significant in mean duration of pauses, empty pauses, filled pauses, lexical pauses, normalized mean duration of filled pauses and lexical pauses. The findings reported in the current paper help characterize the nature of language processing in seniors with or without AD, and contribute to the interactions between the AD neural mechanism and their temporal parameters.

Keywords: language processing, Alzheimer’s disease, Mandarin Chinese, temporal cues

Procedia PDF Downloads 358
2840 Expression of ULK-1 mRNA in Human Peripheral Blood Mononuclear Cells from Patients with Alzheimer's Disease

Authors: Ali Bayram, Remzi Yiğiter

Abstract:

Objective: Alzheimer's disease (AD), the most common cause of dementia, is a progressive neurodegenerative disease. At present, diagnosis of AD is rather late in the disease. Therefore, we attempted to find peripheral biomarkers for the early diagnosis of AD. Herein, we conducted a study to investigate the unc-51 like autophagy activating kinase-1 (ULK1) mRNA expression levels in human peripheral blood mononuclear cells from patients with Alzheimer's disease. Method: To determine whether ULK1 gene expression are altered in AD patients, we measured their gene expression in human peripheral blood cell in 50 patients with AD and 50 age and gender matched healthy controls by quantitative real-time PCR technique. Results: We found that both ULK1 gene expression in peripheral blood cell were significantly decreased in patients with AD as compared with controls (p <0.05). Lower levels of ULK1 gene expression were significantly associated with the increased risk for AD. Conclusions: Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2, and PRKAG1, leading to negatively regulate AMPK activity. May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences. Plays a role early in neuronal differentiation and is required for granule cell axon formation. Alzheimer is the most common neurodegenerative disease. Our results provide useful information that the ULK1 gene expression is decreased in the neurodegeneration and AD patients with, indicating their possible systemic involvement in AD.

Keywords: Alzheimer’s sisease, ULK1, mRNA expression, RT-PCR

Procedia PDF Downloads 286
2839 The Interaction between Blood-Brain Barrier and the Cerebral Lymphatics Proposes Therapeutic Method for Alzheimer’S Disease

Authors: M. Klimova, O. Semyachkina-Glushkovskaya, J. Kurts, E. Zinchenko, N. Navolokin, A. Shirokov, A. Dubrovsky, A. Abdurashitov, A. Terskov, A. Mamedova, I. Agranovich, T. Antonova, I. Blokhina

Abstract:

The direction for research of Alzheimer's disease is to find an effective non-invasive and non-pharmacological way of treatment. Here we tested our hypothesis that the opening of the blood-brain barrier (BBB) induces activation of lymphatic drainage and clearing functions that can be used as a method for non-invasive stimulation of clearance of beta-amyloid and therapy of Alzheimer’s disease (AD). To test our hypothesis, in this study on healthy male mice we analyzed the interaction between BBB opening by repeated loud music (100-10000 Hz, 100 dB, duration 2 h: 60 sec – sound; 60 sec - pause) and functional changes in the meningeal lymphatic vessels (MLVs). We demonstrate clearance of dextran 70 kDa (i.v. injection), fluorescent beta-amyloid (intrahippocampal injection) and gold nanorods (intracortical injection) via MLV that significantly increased after the opening of BBB. Our studies also demonstrate that the BBB opening was associated with the improvement of neurocognitive status in mice with AD. Thus, we uncover therapeutic effects of BBB opening by loud music, such as non-invasive stimulation of lymphatic clearance of beta-amyloid in mice with AD, accompanied by improvement of their neurocognitive status. Our data are consistent with other results suggesting the therapeutic effect of BBB opening by focused ultrasound without drugs for patients with AD. This research was supported by a grant from RSF 18-75-10033

Keywords: Alzheimer's disease, beta-amyloid, blood-brain barrier, meningeal lymphatic vessels, repeated loud music

Procedia PDF Downloads 62
2838 Prediction of Alzheimer's Disease Based on Blood Biomarkers and Machine Learning Algorithms

Authors: Man-Yun Liu, Emily Chia-Yu Su

Abstract:

Alzheimer's disease (AD) is the public health crisis of the 21st century. AD is a degenerative brain disease and the most common cause of dementia, a costly disease on the healthcare system. Unfortunately, the cause of AD is poorly understood, furthermore; the treatments of AD so far can only alleviate symptoms rather cure or stop the progress of the disease. Currently, there are several ways to diagnose AD; medical imaging can be used to distinguish between AD, other dementias, and early onset AD, and cerebrospinal fluid (CSF). Compared with other diagnostic tools, blood (plasma) test has advantages as an approach to population-based disease screening because it is simpler, less invasive also cost effective. In our study, we used blood biomarkers dataset of The Alzheimer’s disease Neuroimaging Initiative (ADNI) which was funded by National Institutes of Health (NIH) to do data analysis and develop a prediction model. We used independent analysis of datasets to identify plasma protein biomarkers predicting early onset AD. Firstly, to compare the basic demographic statistics between the cohorts, we used SAS Enterprise Guide to do data preprocessing and statistical analysis. Secondly, we used logistic regression, neural network, decision tree to validate biomarkers by SAS Enterprise Miner. This study generated data from ADNI, contained 146 blood biomarkers from 566 participants. Participants include cognitive normal (healthy), mild cognitive impairment (MCI), and patient suffered Alzheimer’s disease (AD). Participants’ samples were separated into two groups, healthy and MCI, healthy and AD, respectively. We used the two groups to compare important biomarkers of AD and MCI. In preprocessing, we used a t-test to filter 41/47 features between the two groups (healthy and AD, healthy and MCI) before using machine learning algorithms. Then we have built model with 4 machine learning methods, the best AUC of two groups separately are 0.991/0.709. We want to stress the importance that the simple, less invasive, common blood (plasma) test may also early diagnose AD. As our opinion, the result will provide evidence that blood-based biomarkers might be an alternative diagnostics tool before further examination with CSF and medical imaging. A comprehensive study on the differences in blood-based biomarkers between AD patients and healthy subjects is warranted. Early detection of AD progression will allow physicians the opportunity for early intervention and treatment.

Keywords: Alzheimer's disease, blood-based biomarkers, diagnostics, early detection, machine learning

Procedia PDF Downloads 253
2837 Identification of Potential Small Molecule Regulators of PERK Kinase

Authors: Ireneusz Majsterek, Dariusz Pytel, J. Alan Diehl

Abstract:

PKR-like ER kinase (PERK) is serine/threonie endoplasmic reticulum (ER) transmembrane kinase activated during ER-stress. PERK can activate signaling pathways known as unfolded protein response (UPR). Attenuation of translation is mediated by PERK via phosphorylation of eukaryotic initiation factor 2α (eIF2α), which is necessary for translation initiation. PERK activation also directly contributes to activation of Nrf2 which regulates expression of anti-oxidant enzymes. An increased phosphorylation of eIF2α has been reported in Alzheimer disease (AD) patient hippocampus, indicating that PERK is activated in this disease. Recent data have revealed activation of PERK signaling in non-Hodgkins lymphomas. Results also revealed that loss of PERK limits mammary tumor cell growth in vitro and in vivo. Consistent with these observations, activation of UPR in vitro increases levels of the amyloid precursor protein (APP), the peptide from which beta-amyloid plaques (AB) fragments are derived. Finally, proteolytic processing of APP, including the cleavages that produce AB, largely occurs in the ER, and localization coincident with PERK activity. Thus, we expect that PERK-dependent signaling is critical for progression of many types of diseases (human cancer, neurodegenerative disease and other). Therefore, modulation of PERK activity may be a useful therapeutic target in the treatment of different diseases that fail to respond to traditional chemotherapeutic strategies, including Alzheimer’s disease. Our goal will be to developed therapeutic modalities targeting PERK activity.

Keywords: PERK kinase, small molecule inhibitor, neurodegenerative disease, Alzheimer’s disease

Procedia PDF Downloads 422
2836 Clustering-Based Detection of Alzheimer's Disease Using Brain MR Images

Authors: Sofia Matoug, Amr Abdel-Dayem

Abstract:

This paper presents a comprehensive survey of recent research studies to segment and classify brain MR (magnetic resonance) images in order to detect significant changes to brain ventricles. The paper also presents a general framework for detecting regions that atrophy, which can help neurologists in detecting and staging Alzheimer. Furthermore, a prototype was implemented to segment brain MR images in order to extract the region of interest (ROI) and then, a classifier was employed to differentiate between normal and abnormal brain tissues. Experimental results show that the proposed scheme can provide a reliable second opinion that neurologists can benefit from.

Keywords: Alzheimer, brain images, classification techniques, Magnetic Resonance Images MRI

Procedia PDF Downloads 227
2835 Analyzing the Performance of Machine Learning Models to Predict Alzheimer's Disease and its Stages Addressing Missing Value Problem

Authors: Carlos Theran, Yohn Parra Bautista, Victor Adankai, Richard Alo, Jimwi Liu, Clement G. Yedjou

Abstract:

Alzheimer's disease (AD) is a neurodegenerative disorder primarily characterized by deteriorating cognitive functions. AD has gained relevant attention in the last decade. An estimated 24 million people worldwide suffered from this disease by 2011. In 2016 an estimated 40 million were diagnosed with AD, and for 2050 is expected to reach 131 million people affected by AD. Therefore, detecting and confirming AD at its different stages is a priority for medical practices to provide adequate and accurate treatments. Recently, Machine Learning (ML) models have been used to study AD's stages handling missing values in multiclass, focusing on the delineation of Early Mild Cognitive Impairment (EMCI), Late Mild Cognitive Impairment (LMCI), and normal cognitive (CN). But, to our best knowledge, robust performance information of these models and the missing data analysis has not been presented in the literature. In this paper, we propose studying the performance of five different machine learning models for AD's stages multiclass prediction in terms of accuracy, precision, and F1-score. Also, the analysis of three imputation methods to handle the missing value problem is presented. A framework that integrates ML model for AD's stages multiclass prediction is proposed, performing an average accuracy of 84%.

Keywords: alzheimer's disease, missing value, machine learning, performance evaluation

Procedia PDF Downloads 63
2834 Serum Levels of Plasminogen Activator Inhibitor-1 (PAI-1) Are Increased in Alzheimer’s Disease and MCI Patients and Correlate With Cognitive Deficits

Authors: Francesco Angelucci, Katerina Veverova, Alžbeta Katonová, Lydia Piendel, Martin Vyhnalek, Jakub Hort

Abstract:

Alzheimer's disease (AD) is a central nervous system (CNS) disease characterized by loss of memory, cognitive functions and neurodegeneration. Plasmin is an enzyme degrading many plasma proteins. In the CNS, plasmin may reduce the accumulation of A, and have other actions relevant to AD pathophysiology. Brain plasmin synthesis is regulated by two enzymes: one activating, the tissue plasminogen activator (tPA), and the other inhibiting, the plasminogen activator inhibitor-1 (PAI-1). We investigated whether tPA and PAI-1 serum levels in AD and amnestic mild cognitive impairment (aMCI) patients are altered compared to cognitively healthy controls. Moreover, we examined the PAI-1/tPA ratio in these patient groups. 40 AD, 40 aMCI and 10 healthy controls were recruited. Venous blood was collected and PAI-1 and tPA serum concentrations were quantified by sandwich ELISAs. The results showed that PAI-1 levels increased in AD and aMCI patients. This increase negatively correlated with cognitive deficit measured by MMSE. Similarly, the ratio between tPA and PAI-1 gradually increases in aMCI and AD patients. This study demonstrates that AD and aMCI patients have altered PAI-1 serum levels and PAI-1/tPA ratio. Since these enzymes are CNS regulators of plasmin, PAI-1 serum levels could be a marker reflecting a cognitive decline in AD.

Keywords: Alzheimer disease, amnestic mild cognitive impairment, plasmin, tissue-type plasminogen activator

Procedia PDF Downloads 1
2833 Muscle Relaxant Dantrolene Repurposed to Treat Alzheimer's Disease

Authors: Huafeng Wei

Abstract:

Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.

Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis

Procedia PDF Downloads 125
2832 GABARAPL1 (GEC1) mRNA Expression Levels in Patients with Alzheimer's Disease

Authors: Ali Bayram, Burak Uz, Ilhan Dolasik, Remzi Yiğiter

Abstract:

The GABARAP (GABAA-receptor-associated protein) family consists of GABARAP, GABARAPL1 (GABARAP-like 1) and GABARAPL2 (GABARAP-like 2). GABARAPL1, like GABARAP, was described to interact with both GABAA receptor and tubulin, and to be involved in intracellular GABAA receptor trafficking and promoting tubulin polymerization. In addition, GABARAPL1 is thought to be involved in various physiological (autophagosome closure, regulation of circadian rhythms) and/or pathological mechanisms (cancer, neurodegeneration). Alzheimer’s disease (AD) is a progressive neuro degenerative disorder characterized with impaired cognitive functions. Disruption of the GABAergic neuro transmission as well as cholinergic and glutamatergic interactions, may also be involved in the pathogenesis of AD. GABARAPL1 presents a regulated tissue expression and is the most expressed gene among the GABARAP family members in the central nervous system. We, herein, conducted a study to investigate the GABARAPL1 mRNA expression levels in patients with AD. 50 patients with AD and 49 control patients were enrolled to the present study. Messenger RNA expression levels of GABARAPL1 were detected by real-time polymerase chain reaction. GABARAPL1 mRNA expression in AD / control patients was 0,495 (95% confidence interval: 0,404-0,607), p= 0,00000002646. Reduced activity of GABARAPL1 gene might play a role, at least partly, in the pathophysiology of AD.

Keywords: Alzheimer’s disease, GABARAPL1, mRNA expression, RT-PCR

Procedia PDF Downloads 381
2831 In vitro and in vivo Assessment of Cholinesterase Inhibitory Activity of the Bark Extracts of Pterocarpus santalinus L. for the Treatment of Alzheimer’s Disease

Authors: K. Biswas, U. H. Armin, S. M. J. Prodhan, J. A. Prithul, S. Sarker, F. Afrin

Abstract:

Alzheimer’s disease (AD) (a progressive neurodegenerative disorder) is mostly predominant cause of dementia in the elderly. Prolonging the function of acetylcholine by inhibiting both acetylcholinesterase and butyrylcholinesterase is most effective treatment therapy of AD. Traditionally Pterocarpus santalinus L. is widely known for its medicinal use. In this study, in vitro acetylcholinesterase inhibitory activity was investigated and methanolic extract of the plant showed significant activity. To confirm this activity (in vivo), learning and memory enhancing effects were tested in mice. For the test, memory impairment was induced by scopolamine (cholinergic muscarinic receptor antagonist). Anti-amnesic effect of the extract was investigated by the passive avoidance task in mice. The study also includes brain acetylcholinesterase activity. Results proved that scopolamine induced cognitive dysfunction was significantly decreased by administration of the extract solution, in the passive avoidance task and inhibited brain acetylcholinesterase activity. These results suggest that bark extract of Pterocarpus santalinus can be better option for further studies on AD via their acetylcholinesterase inhibitory actions.

Keywords: Pterocarpus santalinus, cholinesterase inhibitor, passive avoidance, Alzheimer’s disease

Procedia PDF Downloads 146
2830 Analysis of NMDA Receptor 2B Subunit Gene (GRIN2B) mRNA Expression in the Peripheral Blood Mononuclear Cells of Alzheimer's Disease Patients

Authors: Ali̇ Bayram, Semih Dalkilic, Remzi Yigiter

Abstract:

N-methyl-D-aspartate (NMDA) receptor is a subtype of glutamate receptor and plays a pivotal role in learning, memory, neuronal plasticity, neurotoxicity and synaptic mechanisms. Animal experiments were suggested that glutamate-induced excitotoxic injuriy and NMDA receptor blockage lead to amnesia and other neurodegenerative diseases including Alzheimer’s disease (AD), Huntington’s disease, amyotrophic lateral sclerosis. Aim of this study is to investigate association between NMDA receptor coding gene GRIN2B expression level and Alzheimer disease. The study was approved by the local ethics committees, and it was conducted according to the principles of the Declaration of Helsinki and guidelines for the Good Clinical Practice. Peripheral blood was collected 50 patients who diagnosed AD and 49 healthy control individuals. Total RNA was isolated with RNeasy midi kit (Qiagen) according to manufacturer’s instructions. After checked RNA quality and quantity with spectrophotometer, GRIN2B expression levels were detected by quantitative real time PCR (QRT-PCR). Statistical analyses were performed, variance between two groups were compared with Mann Whitney U test in GraphpadInstat algorithm with 95 % confidence interval and p < 0.05. After statistical analyses, we have determined that GRIN2B expression levels were down regulated in AD patients group with respect to control group. But expression level of this gene in each group was showed high variability. İn this study, we have determined that NMDA receptor coding gene GRIN2B expression level was down regulated in AD patients when compared with healthy control individuals. According to our results, we have speculated that GRIN2B expression level was associated with AD. But it is necessary to validate these results with bigger sample size.

Keywords: Alzheimer’s disease, N-methyl-d-aspartate receptor, NR2B, GRIN2B, mRNA expression, RT-PCR

Procedia PDF Downloads 302
2829 Rational Design of Potent Compounds for Inhibiting Ca2+ -Dependent Calmodulin Kinase IIa, a Target of Alzheimer’s Disease

Authors: Son Nguyen, Thanh Van, Ly Le

Abstract:

Ca2+ - dependent calmodulin kinase IIa (CaMKIIa) has recently been found to associate with protein tau missorting and polymerization in Alzheimer’s Disease (AD). However, there has yet inhibitors targeting CaMKIIa to investigate the correlation between CaMKIIa activity and protein tau polymer formation. Combining virtual screening and our statistics in binding contribution scoring function (BCSF), we rationally identified potential compounds that bind to specific CaMKIIa active site and specificity-affinity distribution of the ligand within the active site. Using molecular dynamics simulation, we identified structural stability of CaMKIIa and potent inhibitors, and site-directed bonding, separating non-specific and specific molecular interaction features. Despite of variation in confirmation of simulation time, interactions of the potent inhibitors were found to be strongly associated with the unique chemical features extracted from molecular binding poses. In addition, competitive inhibitors within CaMKIIa showed an important molecular recognition pattern toward specific ligand features. Our approach combining virtual screening with BCSF may provide an universally applicable method for precise identification in the discovery of compounds.

Keywords: Alzheimer’s disease, Ca 2+ -dependent calmodulin kinase IIa, protein tau, molecular docking

Procedia PDF Downloads 153