MR Brain Screening using Optimization Techniques – A survey

2021 ◽  
Vol 17 ◽  
Author(s):  
Chitradevi D ◽  
Prabha S.
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Memory Loss ◽  
Amyloid Β ◽  
Cell Loss ◽  
Optimization Techniques ◽  
Amyloid Β Protein ◽  
The Brain ◽  
Brain Tissues

Background: Alzheimer’s disease (AD) is associated with Dementia, and it is also a memory syndrome in the brain. It affects the brain tissues and causes major changes in day-to-day activities. Aging is a major cause of Alzheimer's disease. AD is characterized by two pathological hallmarks as, Amyloid β protein and neurofibrillary tangles of hyperphosphorylated tau protein. The imaging hallmarks for Alzheimer’s disease are namely, swelling, shrinkage of brain tissues due to cell loss, and atrophy in the brain due to protein dissemination. Based on the survey, 60% to 80% of dementia patients belong to Alzheimer’s disease. Introduction: AD is now becoming an increasing and important brain disease. The goal of AD pathology is to cause changes/damage in brain tissues. Alzheimer's disease is thought to begin 20 years or more before symptoms appear, with tiny changes in the brain that are undetectable to the person affected. The changes in a person's brain after a few years are noticeable through symptoms such as language difficulties and memory loss. Neurons in different parts of the brain have detected symptoms such as cognitive impairments and learning disabilities. In this case, neuroimaging tools are necessary to identify the development of pathology which relates to the clinical symptoms. Methods: Several approaches have been tried during the last two decades for brain screening to analyse AD with the process of pre-processing, segmentation and classification. Different individual such as Grey Wolf optimization, Lion Optimization, Ant Lion Optimization and so on. Similarly, hybrid optimization techniques are also attempted to segment the brain sub-regions which helps in identifying the bio-markers to analyse AD. Conclusion: This study discusses a review of neuroimaging technologies for diagnosing Alzheimer's disease, as well as the discovery of hallmarks for the disease and the methodologies for finding hallmarks from brain images to evaluate AD. According to the literature review, most of the techniques predicted higher accuracy (more than 90%), which is beneficial for assessing and screening neurodegenerative illness, particularly 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 Case of early-onset Alzheimer’s disease with atypical manifestation

2021 ◽  
Vol 34 (1) ◽  
pp. e100283
Author(s):  
Lin Zhu ◽  
Limin Sun ◽  
Lin Sun ◽  
Shifu Xiao
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Manifestation ◽  
Early Onset ◽  
Short Term Memory ◽  
Brain Mri ◽  
Memory Loss ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Fluent Aphasia

Short-term memory decline is the typical clinical manifestation of Alzheimer’s disease (AD). However, early-onset AD usually has atypical symptoms and may get misdiagnosed. In the present case study, we reported a patient who experienced symptoms of memory loss with progressive non-fluent aphasia accompanied by gradual social withdrawal. He did not meet the diagnostic criteria of AD based on the clinical manifestation and brain MRI. However, his cerebrospinal fluid examination showed a decreased level of beta-amyloid 42, and increased total tau and phosphorylated tau. Massive amyloid β-protein deposition by 11C-Pittsburgh positron emission tomography confirmed the diagnosis of frontal variant AD. This case indicated that early-onset AD may have progressive non-fluent aphasia as the core manifestation. The combination of individual and precision diagnosis would be beneficial for similar cases.

scholarly journals A Systematic Review of Glucose Transport Alterations in Alzheimer's Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Natalia Kyrtata ◽  
Hedley C. A. Emsley ◽  
Oli Sparasci ◽  
Laura M. Parkes ◽  
Ben R. Dickie
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glucose Transport ◽  
Clinical Symptoms ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Glucose Transporters ◽  
Rodent Models ◽  
The Brain

Introduction: Alzheimer's disease (AD) is characterized by cerebral glucose hypometabolism. Hypometabolism may be partly due to reduced glucose transport at the blood-brain barrier (BBB) and across astrocytic and neuronal cell membranes. Glucose transporters (GLUTs) are integral membrane proteins responsible for moving glucose from the bloodstream to parenchymal cells where it is metabolized, and evidence indicates vascular and non-vascular GLUTs are altered in AD brains, a process which could starve the brain of glucose and accelerate cognitive decline. Here we review the literature on glucose transport alterations in AD from human and rodent studies.Methods: Literature published between 1st January 1946 and 1st November 2020 within EMBASE and MEDLINE databases was searched for the terms “glucose transporters” AND “Alzheimer's disease”. Human and rodent studies were included while reviews, letters, and in-vitro studies were excluded.Results: Forty-three studies fitting the inclusion criteria were identified, covering human (23 studies) and rodent (20 studies). Post-mortem studies showed consistent reductions in GLUT1 and GLUT3 in the hippocampus and cortex of AD brains, areas of the brain closely associated with AD pathology. Tracer studies in rodent models of AD and human AD also exhibit reduced uptake of glucose and glucose-analogs into the brain, supporting these findings. Longitudinal rodent studies clearly indicate that changes in GLUT1 and GLUT3 only occur after amyloid-β pathology is present, and several studies indicate amyloid-β itself may be responsible for GLUT changes. Furthermore, evidence from human and rodent studies suggest GLUT depletion has severe effects on brain function. A small number of studies show GLUT2 and GLUT12 are increased in AD. Anti-diabetic medications improved glucose transport capacity in AD subjects.Conclusions: GLUT1 and GLUT3 are reduced in hippocampal and cortical regions in patients and rodent models of AD, and may be caused by high levels of amyloid-β in these regions. GLUT3 reductions appear to precede the onset of clinical symptoms. GLUT2 and GLUT12 appear to increase and may have a compensatory role. Repurposing anti-diabetic drugs to modify glucose transport shows promising results in human studies of AD.

scholarly journals A Study of the SORL1 Gene in the Pathogenesis of Late-onset Alzheimer’s Disease by Affecting the Expression of BDNF

2021 ◽  
Author(s):  
Mingri Zhao ◽  
Jiangfeng Liu ◽  
Jingli He ◽  
Xun Chen ◽  
Yanjin Feng ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Cell Model ◽  
Amyloid Β ◽  
Cognitive Disorders ◽  
Amyloid Β Protein ◽  
Bdnf Expression ◽  
The Brain

Abstract BackgroundAlzheimer’s disease is a neurodegenerative disease characterized by progressive memory impairment and other cognitive disorders. It is divided into Familial Alzheimer's disease (FAD) and Sporadic Alzheimer's disease (SAD). SAD is also called delayed Late-onset Alzheimer's disease (LOAD). Sortilin Related Receptor 1 (SORL1) is a high-risk pathogenic gene of LOAD, which can participate in the occurrence and development of AD by affecting the transport and metabolism of intracellular β-amyloid precursor protein (APP). The expression of SORL1 is significantly downregulated in patients with LOAD.ResultsIn the SORL1 knockout (SORL1 KO) mouse model constructed by CRISPR/cas9, we found that the expression of Brain Derived Neurotrophic Factor (BDNF) in the brain of SORL1 KO mice was significantly down-regulated and Amyloid β-protein (Aβ) deposition was found in the brain ofSORL1 KO mice. Through the SORL1 knockdown N2a cell model constructed by shRNA, we also found that when the SORL1 expression was knocked down, the BDNF expression was also downregulated and the cell viability decreased. The results of immunohistochemistry and in vitro cell model experiments suggest that the downregulation of BDNF caused by SORL1 knockdown may be mainly achieved by affecting the expression and distribution of N-Methyl-D-aspartate (NMDAR).ConclusionsSORL1 knockout changes the expression and distribution of NMDAR in cells, downregulates the expression of BDNF, and thus affects the learning and memory of mice.

Probiotic Releasing Angiotensin (1-7) in a Drosophila Model of Alzheimer’s Disease Produces Sex-Specific Effects on Cognitive Function

2021 ◽  
pp. 1-13
Author(s):  
C. Aaron Smith ◽  
Haddon Smith ◽  
Lisa Roberts ◽  
Lori Coward ◽  
Gregory Gorman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
Memory Loss ◽  
Amyloid Β ◽  
Kynurenine Pathway ◽  
Lactobacillus Paracasei ◽  
Amyloid Β Protein ◽  
Complex Disorders ◽  
Model Of Alzheimer’S Disease

Background: While extensive research on the brain has failed to identify effective therapies, using probiotics to target the gut microbiome has shown therapeutic potential in Alzheimer’s disease (AD). Genetically modified probiotics (GMP) are a promising strategy to deliver key therapeutic peptides with high efficacy and tissue specificity. Angiotensin (Ang)-(1-7) levels inversely correlate to AD severity, but its administration is challenging. Our group has successfully established a GMP-based method of Ang-(1-7) delivery. Objective: Since Drosophila represents an excellent model to study the effect of probiotics on complex disorders in a high throughput manner, we tested whether oral supplementation with Lactobacillus paracasei releasing Ang-(1-7) (LP-A) delays memory loss in a Drosophila AD model. Methods: Flies overexpressing the human amyloid-β protein precursor and its β-site cleaving enzyme in neurons were randomized to receive four 24-h doses of Lactobacillus paracasei alone (LP), LP-A or sucrose over 14 days. Memory was assessed via an aversive phototaxic suppression assay. Results: Optimal dilution,1:2, was determined based on palatability. LP-A improved memory in trained AD males but worsened cognition in AD females. LP-supplementation experiments confirmed that Ang-(1-7) conferred additional cognitive benefits in males and was responsible for the deleterious cognitive effects in females. Sex-specific differences in the levels of angiotensin peptides and differential activation of the kynurenine pathway of tryptophan metabolism in response to supplementation may underlie this male-only therapeutic response. Conclusion: In summary, LP-A ameliorated the memory deficits of a Drosophila AD model, but effects were sex-specific. Dosage optimization may be required to address this differential response.

scholarly journals Current Biomarkers for Alzheimer’s Disease: From CSF to Blood

2020 ◽  
Vol 10 (3) ◽  
pp. 85 ◽  
Author(s):  
Kun Zou ◽  
Mohammad Abdullah ◽  
Makoto Michikawa
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Early Stage ◽  
Biological Fluid ◽  
Amyloid Β ◽  
Positron Emission Tomography Imaging ◽  
Tau Proteins ◽  
Csf Biomarkers ◽  
Amyloid Β Protein

Alzheimer’s disease (AD) is the most common cause of dementia and affects a large portion of the elderly population worldwide. Currently, a diagnosis of AD depends on the clinical symptoms of dementia, magnetic resonance imaging to determine brain volume, and positron emission tomography imaging to detect brain amyloid or tau deposition. The best characterized biological fluid markers for AD are decreased levels of amyloid β-protein (Aβ) 42 and increased levels of phosphorylated tau and total tau in cerebrospinal fluid (CSF). However, less invasive and easily detectable biomarkers for the diagnosis of AD, especially at the early stage, are still under development. Here, we provide an overview of various biomarkers identified in CSF and blood for the diagnostics of AD over the last 25 years. CSF biomarkers that reflect the three hallmarks of AD, amyloid deposition, neurofibrillary tangles, and neurodegeneration, are well established. Based on the need to start treatment in asymptomatic people with AD and to screen for AD risk in large numbers of young, healthy individuals, the development of biomarkers for AD is shifting from CSF to blood. Elements of the core pathogenesis of AD in blood, including Aβ42, tau proteins, plasma proteins, or lipids have shown their usefulness and capabilities in AD diagnosis. We also highlight some novel identified blood biomarkers (including Aβ42/Aβ43, p-tau 181, Aβ42/APP669-711, structure of Aβ in blood, and flotillin) for AD.

scholarly journals Defect of branched-chain amino acid metabolism promotes the development of Alzheimer’s disease by targeting the mTOR signaling

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Huajie Li ◽  
Dan Ye ◽  
Wei Xie ◽  
Fei Hua ◽  
Yilin Yang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amino Acid ◽  
Amyloid Β ◽  
Mtor Signaling ◽  
Branched Chain Amino Acid ◽  
Metabolic Defect ◽  
Branched Chain ◽  
The Brain ◽  
Brain Tissues

Diabetes is a risk factor for Alzheimer’s disease (AD) in humans. Branched-chain amino acids (BCAAs, namely valine, leucine, and isoleucine) metabolic defect is observed in human diabetes, which is associated with insulin resistance. But whether BCAAs connect diabetes and AD remains unknown. Here, we show that BCAA metabolic defect may be one of the drivers of AD. BCAA levels were increased in the blood in human patients and mice with diabetes or AD. BCAA-enriched diet promoted the development of AD in mice as evidenced by the behavior and pathological analysis. Branched-chain amino acid transaminase 1 and 2 (BCAT1 and BCAT2) are the two enzymes for the first step metabolism of BCAAs by catalyzing BCAAs to generate branched-chain ketoacids. The expression of Bcat1 but not Bcat2 was significantly down-regulated in the brain tissues of diabetic, aged, and AD mice. Leucine up-regulated the phosphorylation of Tau but not affected the accumulation of amyloid β in the brain tissues or isolated neurons. In addition, knockdown of the expression of Bcat1, which would result in the accumulation of BCAAs, led to the same phenotype as BCAAs supplement in neurons. Interestingly, leucine supplement or Bcat1 knockdown promoted the activation of the mTOR signaling in the brains of AD mice or neurons. Subsequently, mTOR was critically involved in leucine and Bcat1 knockdown-mediated phosphorylation of Tau. Taken together, our findings demonstrated that diabetes-related BCAA accumulation in the brain tissues led to the phosphorylation of Tau and, subsequently, the development of diabetes-related AD.

scholarly journals Applying fluid biomarkers to Alzheimer's disease

2017 ◽  
Vol 313 (1) ◽  
pp. C3-C10 ◽  
Author(s):  
Henrik Zetterberg
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Medial Temporal Lobe ◽  
Clinical Symptoms ◽  
Senile Plaque ◽  
Neurofibrillary Tangle ◽  
Amyloid Β ◽  
Differential Diagnoses ◽  
Blood Tests ◽  
The Brain

Alzheimer’s disease (AD) is a common neurodegenerative disease that starts with a clinically silent phase of a decade or more during which brain pathologies accumulate predominantly in the medial temporal lobe but also elsewhere in the brain. Network dysfunction and clinical symptoms typically appear when senile plaque (amyloid-β) and neurofibrillary tangle (tau) pathologies meet in the brain parenchyma, producing synapse and neuronal loss. For plaque and tangle pathologies, reliable fluid biomarkers have been developed. These require sampling of cerebrospinal fluid. Reliable blood tests for plaque and tangle pathologies are currently lacking, but blood tests for general neurodegeneration have recently been developed. In AD, plaques and tangles often coexist with other pathologies, including Lewy bodies, and to what extent these contribute to symptoms is currently unknown. There are also important differential diagnoses that may be possible to distinguish from AD with the aid of biomarkers. The scope of this review is fluid biomarkers for AD and related pathologies. The purpose is to provide the reader with an updated account of currently available fluid biomarkers for AD and clinically relevant differential diagnoses.

scholarly journals A Super-Resolved View of the Alzheimer’s Disease-Related Amyloidogenic Pathway in Hippocampal Neurons

2021 ◽  
pp. 1-20
Author(s):  
Yang Yu ◽  
Yang Gao ◽  
Bengt Winblad ◽  
Lars Tjernberg ◽  
Sophia Schedin Weiss
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hippocampal Neurons ◽  
Three Dimensional ◽  
Amyloid Β ◽  
Stimulated Emission ◽  
Amyloid Β Peptide ◽  
Primary Neurons ◽  
Amyloid Β Protein ◽  
Early Endosomes

Background: Processing of the amyloid-β protein precursor (AβPP) is neurophysiologically important due to the resulting fragments that regulate synapse biology, as well as potentially harmful due to generation of the 42 amino acid long amyloid β-peptide (Aβ 42), which is a key player in Alzheimer’s disease. Objective: Our aim was to clarify the subcellular locations of the amyloidogenic AβPP processing in primary neurons, including the intracellular pools of the immediate substrate, AβPP C-terminal fragment (APP-CTF) and the product (Aβ 42). To overcome the difficulties of resolving these compartments due to their small size, we used super-resolution microscopy. Methods: Mouse primary hippocampal neurons were immunolabelled and imaged by stimulated emission depletion (STED) microscopy, including three-dimensional, three-channel imaging and image analyses. Results: The first (β-secretase) and second (γ-secretase) cleavages of AβPP were localized to functionally and distally distinct compartments. The β-secretase cleavage was observed in early endosomes, where we were able to show that the liberated N- and C-terminal fragments were sorted into distinct vesicles budding from the early endosomes in soma. Lack of colocalization of Aβ 42 and APP-CTF in soma suggested that γ-secretase cleavage occurs in neurites. Indeed, APP-CTF was, in line with Aβ 42 in our previous study, enriched in the presynapse but absent from the postsynapse. In contrast, full-length AβPP was not detected in either the pre- or the postsynaptic side of the synapse. Furthermore, we observed that endogenously produced and endocytosed Aβ 42 were localized in different compartments. Conclusion: These findings provide critical super-resolved insight into amyloidogenic AβPP processing in primary neurons.

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