scholarly journals A review on treatment of Alzheimer’s disease

2010 ◽  
Vol 2 (1) ◽  
pp. 159-164
Author(s):  
Suman Pratihar ◽  
Shomik Nag ◽  
Jayanta Kumar Kundu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hormonal Treatment ◽  
Amyloid Plaque ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Brain Disorder ◽  
Herbal Products ◽  
Macrophage Activity ◽  
The Brain

Alzheimer’s disease is a brain disorder named after German physician Alois Alzheimer, who first described it in 1906. The Alzheimer’s disease is now becoming curable by identifying the actual cause of the disease with the proper diagnosis of the disease of the patient. The disease can now be cured by drug treatment, by hormonal treatment and by using herbal products such as medicines. The drugs are based on antagonizing action of the components against the causative agents (â Amyloid plaque, Apolipoprotein E, Tau protein) of the disease. Thecommon drugs based on their action are N-methyl-D-aspartate (NMDA) receptor antagonists, Cholinesterase inhibitor, agents for increasing blood supply and neurotransmitter in the brain, lipofuchsin and â Amyloid plaque inhibitor, free radical scavenger, agent for metal chelator and agent for increasing macrophage activity in the brain.

Current Strategies and Novel Drug Approaches for Alzheimer Disease

2020 ◽  
Vol 19 (9) ◽  
pp. 676-690 ◽  
Author(s):  
Roma Ghai ◽  
Kandasamy Nagarajan ◽  
Meenakshi Arora ◽  
Parul Grover ◽  
Nazakat Ali ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinergic Neurons ◽  
Amyloid Plaque ◽  
Neural Pathways ◽  
Current Trends ◽  
Personality Changes ◽  
Traditional Therapies ◽  
Novel Drug ◽  
The Brain

Alzheimer’s Disease (AD) is a chronic, devastating dysfunction of neurons in the brain leading to dementia. It mainly arises due to neuronal injury in the cerebral cortex and hippocampus area of the brain and is clinically manifested as a progressive mental failure, disordered cognitive functions, personality changes, reduced verbal fluency and impairment of speech. The pathology behind AD is the formation of intraneuronal fibrillary tangles, deposition of amyloid plaque and decline in choline acetyltransferase and loss of cholinergic neurons. Tragically, the disease cannot be cured, but its progression can be halted. Various cholinesterase inhibitors available in the market like Tacrine, Donepezil, Galantamine, Rivastigmine, etc. are being used to manage the symptoms of Alzheimer’s disease. The paper’s objective is to throw light not only on the cellular/genetic basis of the disease, but also on the current trends and various strategies of treatment including the use of phytopharmaceuticals and nutraceuticals. Enormous literature survey was conducted and published articles of PubMed, Scifinder, Google Scholar, Clinical Trials.org and Alzheimer Association reports were studied intensively to consolidate the information on the strategies available to combat Alzheimer’s disease. Currently, several strategies are being investigated for the treatment of Alzheimer’s disease. Immunotherapies targeting amyloid-beta plaques, tau protein and neural pathways are undergoing clinical trials. Moreover, antisense oligonucleotide methodologies are being approached as therapies for its management. Phytopharmaceuticals and nutraceuticals are also gaining attention in overcoming the symptoms related to AD. The present review article concludes that novel and traditional therapies simultaneously promise future hope for AD treatment.

Assessment of Graph Metrics and Lateralization of Brain Connectivity in Progression of Alzheimer's Disease Using fMRI

2017 ◽  
Vol 9 (4) ◽  
pp. 46-66 ◽  
Author(s):  
Bhuvaneshwari Bhaskaran ◽  
Kavitha Anandan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Default Mode Network ◽  
Brain Connectivity ◽  
Brain Network ◽  
Brain Disorder ◽  
Default Mode ◽  
Graph Metrics ◽  
Functional Topology ◽  
The Brain

Alzheimer's disease (AD) is a progressive brain disorder which has a long preclinical phase. The beta-amyloid plaques and tangles in the brain are considered as the main pathological causes. Functional connectivity is typically examined in capturing brain network dynamics in AD. A definitive underconnectivity is observed in patients through the progressive stages of AD. Graph theoretic modeling approaches have been effective in understanding the brain dynamics. In this article, the brain connectivity patterns and the functional topology through the progression of Alzheimer's disease are analysed using resting state fMRI. The altered network topology is analysed by graphed theoretical measures and explains cognitive deficits caused by the progression of this disease. Results show that the functional topology is disrupted in the default mode network regions as the disease progresses in patients. Further, it is observed that there is a lack of left lateralization involving default mode network regions as the severity in AD increases.

scholarly journals Alzheimer’s disease under the purview of Graph Theory Centric Genetic Networks

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Yegnanarayanan Venkatraman ◽  
◽  
Narayanaa Y Krithicaa ◽  
Valentina E. Balas ◽  
Marius M. Balas ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Graph Theory ◽  
Network Theory ◽  
Memory Loss ◽  
Amyloid Plaque ◽  
Brain Regions ◽  
Protein Protein Interaction ◽  
Communication Demands ◽  
The Brain

Notice that the synapsis of brain is a form of communication. As communication demands connectivity, it is not a surprise that "graph theory" is a fastest growing area of research in the life sciences. It attempts to explain the connections and communication between networks of neurons. Alzheimer’s disease (AD) progression in brain is due to a deposition and development of amyloid plaque and the loss of communication between nerve cells. Graph/network theory can provide incredible insights into the incorrect wiring leading to memory loss in a progressive manner. Network in AD is slanted towards investigating the intricate patterns of interconnections found in the pathogenesis of brain. Here, we see how the notions of graph/network theory can be prudently exploited to comprehend the Alzheimer’s disease. We begin with introducing concepts of graph/network theory as a model for specific genetic hubs of the brain regions and cellular signalling. We begin with a brief introduction of prevalence and causes of AD followed by outlining its genetic and signalling pathogenesis. We then present some of the network-applied outcome in assessing the disease-signalling interactions, signal transduction of protein-protein interaction, disturbed genetics and signalling pathways as compelling targets of pathogenesis of the disease.

scholarly journals Elevated age-related cortical iron, ferritin and amyloid plaques in APPswe/PS1ΔE9 transgenic mouse model of Alzheimer’s disease

2019 ◽  
pp. S445-S451 ◽  
Author(s):  
H. Svobodová ◽  
D. Kosnáč ◽  
Z. Balázsiová ◽  
H. Tanila ◽  
P.O. Miettinen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Plaques ◽  
Amyloid Plaque ◽  
Free Iron ◽  
Model Of Alzheimer’S Disease ◽  
Age Related ◽  
Concentration Changes ◽  
The Brain ◽  
Important Marker

Iron is very important element for functioning of the brain. Its concentration changes with aging the brain or during disease. The aim of our work was the histological examination of content of ferritin and free iron (unbound) in brain cortex in association with Aβ plaques from their earliest stages of accumulation in amyloid plaque forming APP/PS1 transgenic mice. Light microscopy revealed the onset of plaques formation at 8-monthage. Detectable traces of free iron and no ferritin were found around plaques at this age, while the rate of their accumulation in and around Aβ plaques was elevated at 13 months of age. Ferritin accumulated mainly on the edge of Aβ plaques, while the smaller amount of free iron was observed in the plaque-free tissue, as well as in and around Aβ plaques. We conclude that free iron and ferritin accumulation follows the amyloid plaques formation. Quantification of cortical iron and ferritin content can be an important marker in the diagnosis of Alzheimer’s disease.

scholarly journals Peptide Interference with APP and Tau Association: Relevance to Alzheimer’s Disease Amelioration

2020 ◽  
Vol 21 (9) ◽  
pp. 3270
Author(s):  
Ruth Maron ◽  
Gad Armony ◽  
Michael Tsoory ◽  
Meir Wilchek ◽  
Dan Frenkel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Model ◽  
Amyloid Plaque ◽  
In Vivo Studies ◽  
Nasal Administration ◽  
Plaque Burden ◽  
Cognitive Deficiency ◽  
The Brain

The two major proteins involved in Alzheimer’s disease (AD) are the amyloid precursor protein (APP) and Tau. Here, we demonstrate that these two proteins can bind to each other. Four possible peptides APP1 (390–412), APP2 (713–730), Tau1 (19–34) and Tau2 (331–348), were predicted to be involved in this interaction, with actual binding confirmed for APP1 and Tau1. In vivo studies were performed in an Alzheimer Disease animal model—APP double transgenic (Tg) 5xFAD—as well as in 5xFAD crossed with Tau transgenic 5xFADXTau (FT), which exhibit declined cognitive reduction at four months of age. Nasal administration of APP1 and Tau1 mixture, three times a week for four or five months, reduced amyloid plaque burden as well as the level of soluble Aβ 1–42 in the brain. The treatment prevented the deterioration of cognitive functions when initiated at the age of three months, before cognitive deficiency was evident, and also at the age of six months, when such deficiencies are already observed, leading to a full regain of cognitive function.

scholarly journals Clinically approved IVIg delivered to the hippocampus with focused ultrasound promotes neurogenesis in a model of Alzheimer’s disease

2020 ◽  
Vol 117 (51) ◽  
pp. 32691-32700
Author(s):  
Sonam Dubey ◽  
Stefan Heinen ◽  
Slavica Krantic ◽  
JoAnne McLaurin ◽  
Donald R. Branch ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Effective Dose ◽  
Focused Ultrasound ◽  
Mode Of Delivery ◽  
Amyloid Plaque ◽  
Hippocampal Neurogenesis ◽  
Plaque Pathology ◽  
Bbb Permeability ◽  
The Brain

Preclinical and clinical data support the use of focused ultrasound (FUS), in the presence of intravenously injected microbubbles, to safely and transiently increase the permeability of the blood–brain barrier (BBB). FUS-induced BBB permeability has been shown to enhance the bioavailability of administered intravenous therapeutics to the brain. Ideal therapeutics candidates for this mode of delivery are those capable of inducing benefits peripherally following intravenous injection and in the brain at FUS-targeted areas. In Alzheimer’s disease, intravenous immunoglobulin (IVIg), a fractionated human blood product containing polyclonal antibodies, act as immunomodulator peripherally and centrally, and it can reduce amyloid pathology in the brain. Using the TgCRND8 mouse model of amyloidosis, we tested whether FUS can improve the delivery of IVIg, administered intravenously (0.4 g/kg), to the hippocampus and reach an effective dose to reduce amyloid plaque pathology and promote neurogenesis. Our results show that FUS-induced BBB permeability is required to deliver a significant amount of IVIg (489 ng/mg) to the targeted hippocampus of TgCRN8 mice. Two IVIg-FUS treatments, administered at days 1 and 8, significantly increased hippocampal neurogenesis by 4-, 3-, and 1.5-fold in comparison to saline, IVIg alone, and FUS alone, respectively. Amyloid plaque pathology was significantly reduced in all treatment groups: IVIg alone, FUS alone, and IVIg-FUS. Putative factors promoting neurogenesis in response to IVIg-FUS include the down-regulation of the proinflammatory cytokine TNF-α in the hippocampus. In summary, FUS was required to deliver an effective dose of IVIg to promote hippocampal neurogenesis and modulate the inflammatory milieu.

Carbon Nano Tubes: Novel drug delivery system in amelioration of Alzheimer’s disease

2020 ◽  
Vol 23 ◽  
Author(s):  
Jayanti Mishra ◽  
Bhumika Kumar ◽  
Mukesh Pandey ◽  
Faheem Hyder Pottoo ◽  
Faizana Fayaz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Carbon Nanotubes ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Drug Delivery System ◽  
Delivery System ◽  
Drug Loading ◽  
Brain Disorder ◽  
Biological Barriers ◽  
The Brain

Background: Alzheimer’s disease is an irreversible, progressive brain disorder manifested with symptoms like loss of memory (known as dementia), personality changes, loss of cognition, impaired movement, confusion, deteriorated planning and thought process. Neurodegeneration in Alzheimer’s disease is the result of deposition of protein beta-amyloid that forms plaques and another protein called tau, forming tangles that prevent proper functioning of nerve cells in the brain. Methods: The goal of the review was to comprehensively study the utilization of nanotechnology and the role that carbon nanotubes can play as a drug delivery system for amelioration of Alzheimer’s disease. Results: Nanotechnology is one of the most researched domains of modern science. It contributes significantly to therapeutics by facilitating drug therapy to reach the target sites, which are otherwise difficult to reach with conventional drug delivery systems. Carbon nanotubes are the allotropes of carbon in which several carbon atoms bind with each other to form a cylindrical or a tube-like structure. The carbon nanotubes possess several unique qualities, which confers them with a high potential of being utilized as an efficient drug delivery system. They offer high drug loading, can readily cross the toughest biological barriers like BBB. Carbon nanotubes also facilitate the passage of drugs to the brain via the olfactory route, which further helps in restoring normal autophagy, thus preventing the elimination of autophagic chemicals. They can carry a vast range of cargos, including drugs, antigens, genetic materials, and biological macromolecules. Conclusion: Carbon nanotubes are highly promising drug delivery system for anti-Alzheimer’s drugs. They have potential of overcoming the various biological barriers like BBB. However, more extensive research is required so as to set up a firm base for development of advanced commercial products based on carbon nanotubes for treatment of Alzheimer’s disease.

Assessment of Graph Metrics and Lateralization of Brain Connectivity in Progression of Alzheimer's Disease Using fMRI

2021 ◽  
pp. 589-610
Author(s):  
Bhuvaneshwari Bhaskaran ◽  
Kavitha Anandan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Default Mode Network ◽  
Brain Connectivity ◽  
Brain Network ◽  
Brain Disorder ◽  
Default Mode ◽  
Graph Theoretic ◽  
Functional Topology ◽  
The Brain

Alzheimer's disease (AD) is a progressive brain disorder which has a long preclinical phase. The beta-amyloid plaques and tangles in the brain are considered as the main pathological causes. Functional connectivity is typically examined in capturing brain network dynamics in AD. A definitive underconnectivity is observed in patients through the progressive stages of AD. Graph theoretic modeling approaches have been effective in understanding the brain dynamics. In this article, the brain connectivity patterns and the functional topology through the progression of Alzheimer's disease are analysed using resting state fMRI. The altered network topology is analysed by graphed theoretical measures and explains cognitive deficits caused by the progression of this disease. Results show that the functional topology is disrupted in the default mode network regions as the disease progresses in patients. Further, it is observed that there is a lack of left lateralization involving default mode network regions as the severity in AD increases.

scholarly journals CERTL Reduces C16 Ceramide, Amyloid-β Levels and Inflammation in a Model of Alzheimer's Disease

2020 ◽  
Author(s):  
Simone Mwenda Crivelli ◽  
Qian Luo ◽  
Jo Stevens ◽  
Caterina Giovagnoni ◽  
Daan van Kruining ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuroblastoma Cells ◽  
Amyloid Β ◽  
Amyloid Plaque ◽  
Model Of Alzheimer’S Disease ◽  
Aβ Aggregation ◽  
The Brain

Abstract Background: Deregulation of ceramide and sphingomyelin levels have been suggested to contribute to the pathogenesis of Alzheimer’s disease (AD). Ceramide transfer proteins (CERTs) are ceramide carriers, crucial for ceramide and sphingomyelin balance in cells. Extracellular forms of CERTs co-localize with amyloid-β (Aβ) plaques in AD brains. To date, the significance of these observations for the pathophysiology of AD remains uncertain.Methods: The plasmid expressing CERTL, the long isoform of CERTs, was used to study the interaction of CERTL with amyloid precursor protein (APP) by co-immunoprecipitation and immunofluorescence in HEK cells. The recombinant CERTL protein was employed to study interaction of CERTL with amyloid-β (Aβ), Aβ aggregation process in presence of CERTL, and the resulting changes in Aβ toxicity in neuroblastoma cells. CERTL was overexpressed in neurons by adeno associated virus (AAV) in a familial mouse model of familial AD (5xFAD). Ten weeks after transduction animal were challenged with behavior tests for memory, anxiety and locomotion. At week twelve brains were investigated for sphingolipid levels by mass spectrometry, plaques and neuroinflammation by immunohistochemistry, gene expression and/or immunoassay.Results: Here, we report that CERTL, binds to APP, modifies Aβ aggregation and reduces Aβ neurotoxicity in vitro. Furthermore, we show that intracortical injection of AAV, mediating the expression of CERTL, decreases levels of ceramide d18:1/16:0 and increases sphingomyelin levels in the brain of male transgenic mice, modelling familial AD (5xFAD). CERTL in vivo over-expression has a mild effect on animal locomotion and decreases Aβ formation and modulates microglia by decreasing their pro-inflammatory phenotype.Conclusion: Our results demonstrate a crucial role of CERTL in regulating ceramide levels in the brain, in amyloid plaque formation and neuroinflammation, thereby opening research avenues for therapeutic targets of AD and other neurodegenerative diseases.

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