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.

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 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.

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 The Dynamics of β-Amyloid Proteoforms Accumulation in the Brain of a 5xFAD Mouse Model of Alzheimer’s Disease

2021 ◽  
Vol 23 (1) ◽  
pp. 27
Author(s):  
Anna E. Bugrova ◽  
Polina A. Strelnikova ◽  
Maria I. Indeykina ◽  
Alexey S. Kononikhin ◽  
Natalia V. Zakharova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Senile Plaques ◽  
The Elderly ◽  
Mobility Separation ◽  
Model Of Alzheimer’S Disease ◽  
Β Amyloid ◽  
Ion Mobility Separation ◽  
The Brain

Alzheimer’s disease (AD) is the leading cause of dementia among the elderly. Neuropathologically, AD is characterized by the deposition of a 39- to 42-amino acid long β-amyloid (Aβ) peptide in the form of senile plaques. Several post-translational modifications (PTMs) in the N-terminal domain have been shown to increase the aggregation and cytotoxicity of Aβ, and specific Aβ proteoforms (e.g., Aβ with isomerized D7 (isoD7-Aβ)) are abundant in the senile plaques of AD patients. Animal models are indispensable tools for the study of disease pathogenesis, as well as preclinical testing. In the presented work, the accumulation dynamics of Aβ proteoforms in the brain of one of the most widely used amyloid-based mouse models (the 5xFAD line) was monitored. Mass spectrometry (MS) approaches, based on ion mobility separation and the characteristic fragment ion formation, were applied. The results indicated a gradual increase in the Aβ fraction of isoD7-Aβ, starting from approximately 8% at 7 months to approximately 30% by 23 months of age. Other specific PTMs, in particular, pyroglutamylation, deamidation, and oxidation, as well as phosphorylation, were also monitored. The results for mice of different ages demonstrated that the accumulation of Aβ proteoforms correlate with the formation of Aβ deposits. Although the mouse model cannot be a complete analogue of the processes occurring in the human brain in AD, and several of the observed parameters differ significantly from human values supposedly due to the limited lifespan of the model animals, this dynamic study provides evidence on at least one of the possible mechanisms that can trigger amyloidosis in AD, i.e., the hypothesis on the relationship between the accumulation of isoD7-Aβ and the progression of AD-like pathology.

scholarly journals Genetics of Alzheimer’s disease

2021 ◽  
Author(s):  
Theresa König ◽  
Elisabeth Stögmann
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Disease Risk ◽  
Memory Function ◽  
The Elderly ◽  
Genetic Studies ◽  
Genetic Features ◽  
Definition Of ◽  
The Individual

SummaryAlzheimer’s disease (AD) is the leading cause of neurodegeneration in the elderly and is clinically characterized by slowly progressing cognitive decline, which most commonly affects episodic memory function. This eventually leads to difficulties in activities of daily living. Biomarker studies show that the underlying pathology of AD begins 20 years before clinical symptoms. This results in the need to define specific targets and preclinical stages in order to address the problems of this disease at an earlier point in time. Genetic studies are indispensable for gaining insight into the etiology of neurodegenerative diseases and can play a major role in the early definition of the individual disease risk. This review provides an overview of the currently known genetic features of AD.

scholarly journals Non-Alzheimer's disease-related memory impairment and dementia

2013 ◽  
Vol 15 (4) ◽  
pp. 465-473 ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Impairment ◽  
Clinical Symptoms ◽  
Memory Function ◽  
The Elderly ◽  
Memory Deficits ◽  
Common Cause ◽  
Underlying Causes ◽  
Therapeutic Possibilities

Although Alzheimer's disease (AD) is a common cause of memory impairment and dementia in the elderly disturbed memory function is a widespread subjective and/or objective symptom in a variety of medical conditions. The early detection and correct distinction of AD from non-AD memory impairment is critically important to detect possibly treatable and reversible underlying causes. In the context of clinical research, it is crucial to correctly distinguish between AD or non-AD memory impairment in order to build homogenous study populations for the assessment of new therapeutic possibilities. The distinction of AD from non-AD memory impairment may be difficult, especially in mildly affected patients, due to an overlap of clinical symptoms and biomarker alterations between AD and certain non-AD conditions. This review aims to describe recent aspects of the differential diagnosis of AD and non-AD related memory impairment and how these may be considered in the presence of memory deficits.

scholarly journals In silico study of ginsenoside analogues as possible BACE1 inhibitors involved in Alzheimer's disease

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1169
Author(s):  
Neyder Contreras-Puentes ◽  
Jairo Mercado-Camargo ◽  
Antistio Alvíz-Amador
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Clinical Symptoms ◽  
Specific Treatment ◽  
Data Bank ◽  
The Elderly ◽  
Wide Range ◽  
In Silico Study ◽  
Protein Data Bank Database

Background: Neurodegenerative disorders such as Alzheimer's disease show an alarming prevalence in the population, with around 50 million affected individuals worldwide, and is associated with the development of dementia, mainly affecting the elderly population. Currently, the treatments used are based on slowing the progression of the clinical symptoms of Alzheimer’s; however, no specific treatment has been found that induces reversion of the disease. Natural products may induce a wide range of palliative effects, such as ginseng (Panax ginseng), which produces secondary metabolites called ginsenosides, which have multiple therapeutic applications, including for neurodegenerative diseases such as Alzheimer’s. Methods: A virtual screening was carried out, using the CHEMBL database to find analogs of ginsenosides based on the ginsenoside Rg1 (CHEMBL501637). Next, the molecules were optimized and their format modified. The structure of BACE1 was downloaded from the Protein Data Bank database (ID: 1FKN) and prepared for the development of molecular docking using the PyRx software. A database of the ligands was created and molecular docking experiments were carried out, obtaining affinity energy values ​​in Kcal/mol. Results: Of the 27 analogues studied, it was found that the molecules CHEMBL451292, CHEMBL510371 and CHEMBL503302 showed considerable affinity with BACE1 when compared with the reference molecules (verubecestat and donepezil). These affinity energy values for CHEMBL451292, CHEMBL510371 and CHEMBL503302 ​​were -9.6, -8.1 and -7.6 Kcal/mol, respectively. Likewise, the binding site of the ligands to BACE1 were identified, with the main interactions being van der Waals and hydrogen bonding. Conclusions: Three ginsenoside analogues showed a similar binding energy with BACE1 compared to the reference drugs. The residues involved in the inhibitory activity of BACE1 and the type of predominant interactions were identified, which agreed with previous reports.

scholarly journals The Role of Aβ in the Development of Alzheimer’s Disease and its Mechanisms

2020 ◽  
Vol 218 ◽  
pp. 03041
Author(s):  
Yifei Jin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Elderly Population ◽  
Clinical Symptoms ◽  
Senile Plaques ◽  
The Elderly ◽  
Aβ Peptides ◽  
Hyperphosphorylated Tau Protein ◽  
Neurodegenerative Dementia

Alzheimer’s disease (AD) is chronic neurodegenerative dementia representing the most common cause of dementia in the elderly population. It is a major source of morbidity, mortality, and healthcare expenditure worldwide. Although the molecular and cellular properties related to AD have been demonstrated decades before the onset of clinical symptoms, AD’s pathogenesis is still unknown as a combination of risk factors causes it. Today, pathogenesis theories focused on senile plaques (SP) formed by the extracellular accumulation and deposition of Aβ peptides and neurofibrillary tangles (NFTs), which are composed of the hyperphosphorylated tau protein. Furthermore, growing evidence points out that toxic Aβ plays a primary causal role in the induction and transmission of pathology and neuronal dysfunction and loss. Therefore, Aβ is crucial to the development of AD and is a noteworthy issue in AD research. This review shows the formation of Aβ and the differences of cytotoxicity of its various isoforms and aggregation states. It also summarizes the mechanisms by which Aβ induce AD through its neurotoxicity and state how these mechanisms interact and reinforce each other.

P2-096: COMBINING STRUCTURAL MRI, PROTEOMIC, AND GENETIC ADNI DATA FOR EARLY DETECTION OF ALZHEIMER'S DISEASE VIA RANDOM FOREST CLASSIFIERS

2014 ◽  
Vol 10 ◽  
pp. P506-P506
Author(s):  
Ramon Casanova ◽  
Fang-Chi Hsu ◽  
Bryan J. Neth ◽  
Kaycee M. Sink ◽  
Stephen Rapp ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Random Forest ◽  
Early Detection ◽  
Structural Mri
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