scholarly journals Current Understanding of the Physiopathology, Diagnosis and Therapeutic Approach to Alzheimer’s Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1910
Author(s):  
Victoria García-Morales ◽  
Anabel González-Acedo ◽  
Lucía Melguizo-Rodríguez ◽  
Teresa Pardo-Moreno ◽  
Víctor Javier Costela-Ruiz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pharmacological Treatment ◽  
Therapeutic Approach ◽  
Symptom Control ◽  
Memory Loss ◽  
Amyloid Β ◽  
Acetylcholinesterase Inhibitors ◽  
Diagnostic Procedures ◽  
Diagnostic Methods

Alzheimer’s disease (AD) is the most common cause of dementia. It is characterized by cognitive decline and progressive memory loss. The aim of this review was to update the state of knowledge on the pathophysiological mechanisms, diagnostic methods and therapeutic approach to AD. Currently, the amyloid cascade hypothesis remains the leading theory in the pathophysiology of AD. This hypothesis states that amyloid-β (Aβ) deposition triggers a chemical cascade of events leading to the development of AD dementia. The antemortem diagnosis of AD is still based on clinical parameters. Diagnostic procedures in AD include fluid-based biomarkers such as those present in cerebrospinal fluid and plasma or diagnostic imaging methods. Currently, the therapeutic armory available focuses on symptom control and is based on four pillars: pharmacological treatment where acetylcholinesterase inhibitors stand out; pharmacological treatment under investigation which includes drugs focused on the control of Aβ pathology and tau hyperphosphorylation; treatment focusing on risk factors such as diabetes; or nonpharmacological treatments aimed at preventing development of the disease or treating symptoms through occupational therapy or psychological help. AD remains a largely unknown disease. Further research is needed to identify new biomarkers and therapies that can prevent progression of the pathology.

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.

Targeted delivery of montelukast for treatment of Alzheimer’s disease

2021 ◽  
Vol 20 ◽  
Author(s):  
Ashok K. Datusalia ◽  
Gurpreet Singh ◽  
Nikita Yadav ◽  
Sachin Gaun ◽  
Moumita Manik ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Targeted Delivery ◽  
Symptomatic Relief ◽  
Memory Loss ◽  
Amyloid Β ◽  
Lessons Learned ◽  
Nano Structure ◽  
Substantial Impact ◽  
Structure Lipid

: Alzheimer’s disease (AD) is one of the most common neurodegenerative disease, which affect millions of people worldwide. Accumulation of amyloid-β plaques and hyperphosphorylated neurofibrillary tangles are the key mechanisms involved in the etiopathogenesis of AD, characterized by memory loss and behavioural changes. Effective therapies targeting AD pathogenesis are limited, making it the largest unmet clinical need. Unfortunately, the available drugs provide symptomatic relief and primary care, with no substantial impact on the disease pathology. However, in recent years researchers are working hard on several potential therapeutic targets to combat disease pathogenesis and few drugs have also reached clinical trials. In addition, drugs are being repurposed both in the preclinical and clinical studies for the treatment of AD. For instance, montelukast is most commonly used leukotriene receptor antagonist, for treating asthma and seasonal allergy. Its leukotriene antagonistic action can also be beneficial for the reduction of detrimental effects of leukotriene against neuro-inflammation, an hallmark feature of AD. The available marketed formulations of montelukast present challenges such as poor bioavailability and reduced uptake, reflecting the lack of effectiveness of its desired action in the CNS. While on the other side targeted drug delivery is a satisfactory approach to surpass the challenges associated with the therapeutic agents. This review will discuss the enhancement of montelukast treatment efficacy and its access to CNS, by using new approaches like nano-formulation, nasal gel, solid lipid formulation, nano-structure lipid carrier (NSLC), highlighting lessons learned to target AD pathologies and hurdles that persist.

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 Molecular and Imaging Biomarkers in Alzheimer’s Disease: A Focus on Recent Insights

2020 ◽  
Vol 10 (3) ◽  
pp. 61 ◽  
Author(s):  
Chiara Villa ◽  
Marialuisa Lavitrano ◽  
Elena Salvatore ◽  
Romina Combi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Biological Fluids ◽  
Imaging Techniques ◽  
Amyloid Β ◽  
The Elderly ◽  
Diagnostic Methods ◽  
Imaging Biomarkers ◽  
Attractive Alternative

Alzheimer’s disease (AD) is the most common neurodegenerative disease among the elderly, affecting millions of people worldwide and clinically characterized by a progressive and irreversible cognitive decline. The rapid increase in the incidence of AD highlights the need for an easy, efficient and accurate diagnosis of the disease in its initial stages in order to halt or delay the progression. The currently used diagnostic methods rely on measures of amyloid-β (Aβ), phosphorylated (p-tau) and total tau (t-tau) protein levels in the cerebrospinal fluid (CSF) aided by advanced neuroimaging techniques like positron emission tomography (PET) and magnetic resonance imaging (MRI). However, the invasiveness of these procedures and the high cost restrict their utilization. Hence, biomarkers from biological fluids obtained using non-invasive methods and novel neuroimaging approaches provide an attractive alternative for the early diagnosis of AD. Such biomarkers may also be helpful for better understanding of the molecular mechanisms underlying the disease, allowing differential diagnosis or at least prolonging the pre-symptomatic stage in patients suffering from AD. Herein, we discuss the advantages and limits of the conventional biomarkers as well as recent promising candidates from alternative body fluids and new imaging techniques.

Pharmacological treatment of Alzheimer’s disease

2017 ◽  
Author(s):  
Krishna Chinthapalli
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pharmacological Treatment ◽  
Daily Living ◽  
Disease Process ◽  
Acetylcholinesterase Inhibitors ◽  
Underlying Disease ◽  
Global Function ◽  
Glutamate Antagonist ◽  
The Brain

Pharmacological treatment of Alzheimer’s disease is an important part of management of the condition. There are only four drugs available for treatment of the disease and none halt the disease process, however they have a benefit on cognition, behaviour, activities of daily living, and global function. Acetylcholinesterase inhibitors are thought to work by enhancing cholinergic transmission in the brain and are particularly effective in mild and moderate AD, with recent evidence suggesting donepezil is also effective in severe AD. Memantine is the only glutamate antagonist that is available for AD and is limited for use in moderate or severe AD. The choice of drug depends on route of administration, adverse effects, and medical comorbidities. There is intense research on alternative treatments especially those that may stop the underlying disease process.

scholarly journals Alzheimer’s disease: many failed trials, so where do we go from here?

2020 ◽  
Vol 68 (6) ◽  
pp. 1135-1140 ◽  
Author(s):  
Allison Bethanne Reiss ◽  
Amy D Glass ◽  
Thomas Wisniewski ◽  
Benjamin Wolozin ◽  
Irving H Gomolin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Current Knowledge ◽  
Memory Loss ◽  
Treatment Strategies ◽  
Amyloid Β ◽  
Tau Proteins ◽  
Brain Disorder ◽  
The Central Nervous System ◽  
Progressive Cognitive Impairment

Alzheimer’s disease (AD) is a neurodegenerative brain disorder associated with relentlessly progressive cognitive impairment and memory loss. AD pathology proceeds for decades before cognitive deficits become clinically apparent, opening a window for preventative therapy. Imbalance of clearance and buildup of amyloid β and phosphorylated tau proteins in the central nervous system is believed to contribute to AD pathogenesis. However, multiple clinical trials of treatments aimed at averting accumulation of these proteins have yielded little success, and there is still no disease-modifying intervention. Here, we discuss current knowledge of AD pathology and treatment with an emphasis on emerging biomarkers and treatment strategies.

scholarly journals Identification of small molecule drugs that target apolipoprotein E4‐catalyzed amyloid‐β fibrillization: A new therapeutic approach to Alzheimer’s disease

2021 ◽  
Vol 17 (S9) ◽  
Author(s):  
Noah R Johnson ◽  
Athena Ching‐Jung Wang ◽  
Christina M Coughlan ◽  
Stefan H Sillau ◽  
Esteban M Lucero ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Small Molecule ◽  
Therapeutic Approach ◽  
Amyloid Β ◽  
Apolipoprotein E4 ◽  
Small Molecule Drugs

Extraction of Polysaccharides From Bletilla Striata Using a Modified Low-temperature Method and Evaluation of Their Efficacy Against Alzheimer’s Disease

2021 ◽  
Author(s):  
Yi-Wen Lin ◽  
Chih-Hsiang Fang ◽  
Hung-Hsiang Liao ◽  
Feng Huei Lin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Low Temperature ◽  
Memory Loss ◽  
Amyloid Β ◽  
Ulcer Bleeding ◽  
Bletilla Striata ◽  
Temperature Method

Abstract Background: Amyloid-β (Aβ) peptides play a key role in Alzheimer’s disease (AD), the most common type of dementia. AD is characterized by progressive cognitive and memory loss accompanied by personality changes. Bletilla striata, a traditional Chinese medicine, has been widely used in Eastern Asian countries for alimentary canal damage, ulcer, bleeding, bruises, and burns. in this study, we investigated whether BSP could prevent the ROS from Aβ and the possibility to recover from the disease by memory improvement.Methods: In this study, a polysaccharide from Bletilla striata (BSP) with strong antioxidant and anti-inflammatory properties was extracted following a low-temperature method and tested for its efficacy against AD in vitro using N2a and BV-2 cells and in vivo using AD rats.Results: The characterization of the extracted BSP for its molecular structure and the functional group demonstrated the efficiency of the modified method to retain its bioactivity. In vitro, BSP reduced ROS levels in N2a cells and the expression levels of inflammatory-related genes in BV-2 cells treated with Aβ fibrils. In vivo, BSP recovered the learning memory, ameliorated the morphological damages in the hippocampus and cortex, and reduced the expression of the β-secretase protein in AlCl3-induced AD rats.Conclusions: To the best of our knowledge, this is the first study of BSP applicating in AD. Collectively, these findings demonstrated the efficacy of BSP to prevent and alleviate the effects of AD.

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