Linking Amyloid and Tau Pathology in Alzheimer's Disease: The Role of Membrane Cholesterol in Aβ-Mediated Tau Toxicity: Figure 1.

Wray, Selina; Noble, Wendy

doi:10.1523/jneurosci.2234-09.2009

Cited by 35 publications

(30 citation statements)

References 11 publications

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“…The NFTs in neurons ( F i ) are formed from the hyperphosphorylated tau proteins [4, 6–9], and they are released to the extraceullar space (and are then labeled F 0 ) when the neurons die [4, 10]. Hence, …”

Section: Methodsmentioning

confidence: 99%

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Mathematical model on Alzheimer’s disease

2016

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BackgroundAlzheimer disease (AD) is a progressive neurodegenerative disease that destroys memory and cognitive skills. AD is characterized by the presence of two types of neuropathological hallmarks: extracellular plaques consisting of amyloid β-peptides and intracellular neurofibrillary tangles of hyperphosphorylated tau proteins. The disease affects 5 million people in the United States and 44 million world-wide. Currently there is no drug that can cure, stop or even slow the progression of the disease. If no cure is found, by 2050 the number of alzheimer’s patients in the U.S. will reach 15 million and the cost of caring for them will exceed $ 1 trillion annually.ResultsThe present paper develops a mathematical model of AD that includes neurons, astrocytes, microglias and peripheral macrophages, as well as amyloid β aggregation and hyperphosphorylated tau proteins. The model is represented by a system of partial differential equations. The model is used to simulate the effect of drugs that either failed in clinical trials, or are currently in clinical trials.ConclusionsBased on these simulations it is suggested that combined therapy with TNF- α inhibitor and anti amyloid β could yield significant efficacy in slowing the progression of AD.

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Section: Methodsmentioning

confidence: 99%

“…Tau protein in the central nervous system (CNS) is predominantly expressed in neurons; its main role is to promote microtubles assembly and stability. Glycogen synthase kinase-type 3(GSK-3) is activated by the abnormally produced A β , and it mediates the hyperphosphorylation of tau proteins [4, 6–9]. …”

Section: Introductionmentioning

confidence: 99%

Mathematical model on Alzheimer’s disease

2016

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“…1 The major component of senile plaques is the 39-to 42-residue amyloid-β (Aβ) peptide. Aβ 1-40 is a more abundant species, whereas Aβ 1-42 is a more neurontoxic species.…”

Section: Introductionmentioning

confidence: 99%

Cholesterol Promotes the Interaction of Alzheimer β-Amyloid Monomer with Lipid Bilayer

Zheng

2012

Journal of Molecular Biology

112

117

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“…Aβ peptides are intermediate soluble oligomers that readily aggregate and can be directly synaptotoxic. Aggregates also stimulate an inflammatory response that is blamed for progressive damage through mediator release [9] . NFTs are bundles of paired helical filaments in neuronal cytoplasm, largely containing hyperphosphorylated tau protein as well as ubiquitin and other microtubule-associated molecules [10] .…”

Section: Introductionmentioning

confidence: 99%

Exploring the Effect of <b><i>Phyllanthus emblica</i></b> L. on Cognitive Performance, Brain Antioxidant Markers and Acetylcholinesterase Activity in Rats: Promising Natural Gift for the Mitigation of Alzheimer's Disease

et al. 2016

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Neurodegenerative diseases are incurable and debilitating conditions that result in the progressive degeneration of nerve cells, which affect the cognitive activity. Currently, as a result of multiple studies linking Alzheimer's disease (AD) to oxidative damage, the uses of natural antioxidant to prevent, delay, or enhance the pathological changes underlying the progression of AD has received considerable attention. Therefore, this study was aimed at examining the effect of ethanolic extracts of Phyllanthus emblica (EEPE) ripe (EEPEr) and EEPE unripe (EEPEu) fruits on cognitive functions, brain antioxidant enzymes, and acetylcholinesterase (AChE) activity in rat. The effects of EEPEr and EEPEu fruits (i.e., 100 and 200 mg/kg b.w.) were examined in Swiss albino male rats for 12 days and its effect on cognitive functions, brain antioxidant enzymes, and AChE activity determined. Learning and memory enhancing activity of EEPE fruit was examined by using passive avoidance test and rewarded alternation test. Antioxidant potentiality was evaluated by measuring the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase, reduced glutathione (GSH), glutathione-S-transferase, and the contents of thiobarbituric acid reactive substances (TBARS) in entire brain tissue homogenates. AChE activity was determined using colorimetric method. Administration of the highest dose (i.e., 200 mg/kg b.w.) of EEPEr fruit significantly (p < 0.01) and both lowest and highest doses (i.e., 100 and 200 mg/kg b.w.) of EEPEu fruit markedly (p < 0.05, p < 0.001) increased step-through latency in rats on 6th, 11th, and 12th day with respect to the control group. For aforementioned doses, the percentage of memory retention (MR) was considerably (p < 0.05, p < 0.01) increased in rats on 10th, 11th, and 12th days with respect to the control group. The extract, particularly highest dose (i.e., 200 mg/kg b.w.) of EEPEr fruit markedly (p < 0.05) and lowest and highest doses (i.e., 100 and 200 mg/kg b.w.) of EEPEu fruit significantly (p < 0.01) increased the correct responses in rats on 6th, and 12th day related to the control group. In case of this test, the percentage of MR was significantly (p < 0.05, p < 0.01) increased in rats treated with aforementioned doses on 12th day with respect to the control group. The highest dose (i.e., 200 mg/kg b.w.) of EEPEr fruit suggestively (p < 0.05) and both lowest and highest doses (i.e., 100 and 200 mg/kg b.w.) of EEPEu fruit suggestively (p < 0.05, p < 0.01, p < 0.001) increased the levels of SOD, CAT, GSH, GSH-Px and expressively (p < 0.01) decreased the TBARS level compared to the control group. Treatment with the highest dose (i.e., 200 mg/kg b.w.) of EEPEr fruit significantly (p < 0.05) and both lowest and highest doses (i.e., 100 and 200 mg/kg b.w.) of EEPEu fruit markedly (p < 0.01, p < 0.001) decreased the level of AChE activity compared to that of the control group. The present study shows that EEPE fruit possesses an excel...

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Linking Amyloid and Tau Pathology in Alzheimer's Disease: The Role of Membrane Cholesterol in Aβ-Mediated Tau Toxicity: Figure 1.

Cited by 35 publications

References 11 publications

Mathematical model on Alzheimer’s disease

Mathematical model on Alzheimer’s disease

Cholesterol Promotes the Interaction of Alzheimer β-Amyloid Monomer with Lipid Bilayer

Exploring the Effect of <b><i>Phyllanthus emblica</i></b> L. on Cognitive Performance, Brain Antioxidant Markers and Acetylcholinesterase Activity in Rats: Promising Natural Gift for the Mitigation of Alzheimer's Disease

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