scholarly journals Tumour necrosis factor induces increased production of extracellular amyloid-β- and α-synuclein-containing aggregates by human Alzheimer’s disease neurons

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Daniel R Whiten ◽  
Philip W Brownjohn ◽  
Steven Moore ◽  
Suman De ◽  
Alessio Strano ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Aggregation ◽  
Tumour Necrosis Factor ◽  
Single Molecule ◽  
Tumour Necrosis ◽  
Amyloid Β ◽  
Induced Pluripotent Stem Cell ◽  
Aberrant Protein ◽  
Necrosis Factor

Abstract In addition to increased aberrant protein aggregation, inflammation has been proposed as a key element in the pathogenesis and progression of Alzheimer’s disease. How inflammation interacts with other disease pathways and how protein aggregation increases during disease are not clear. We used single-molecule imaging approaches and membrane permeabilization assays to determine the effect of chronic exposure to tumour necrosis factor, a master proinflammatory cytokine, on protein aggregation in human-induced pluripotent stem cell-derived neurons harbouring monogenic Alzheimer’s disease mutations. We report that exposure of Alzheimer’s disease neurons, but not control neurons, to tumour necrosis factor induces substantial production of extracellular protein aggregates. Aggregates from Alzheimer’s disease neurons are composed of amyloid-β and α-synuclein and induce significant permeabilization of lipid membranes in an assay of pathogenicity. These findings provide support for a causal relationship between two crucial processes in Alzheimer’s disease pathogenesis and suggest that targeting inflammation, particularly tumour necrosis factor, may have beneficial downstream effects on ameliorating aberrant protein aggregation and accumulation.

Tumour necrosis factor-α gene polymorphisms and Alzheimer's disease

2003 ◽  
Vol 350 (1) ◽  
pp. 61-65 ◽  
Author(s):  
Doris Culpan ◽  
Sian H MacGowan ◽  
Julia M Ford ◽  
James A.R Nicoll ◽  
W.Sue Griffin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tumour Necrosis Factor ◽  
Gene Polymorphisms ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Blood-based high sensitivity measurements of beta-amyloid and phosphorylated tau as biomarkers of Alzheimer’s disease: a focused review on recent advances

2021 ◽  
pp. jnnp-2021-327370
Author(s):  
Joyce R. Chong ◽  
Nicholas J. Ashton ◽  
Thomas K. Karikari ◽  
Tomotaka Tanaka ◽  
Michael Schöll ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Single Molecule ◽  
Emerging Technologies ◽  
Amyloid Β ◽  
High Sensitivity ◽  
Phosphorylated Tau ◽  
Meso Scale Discovery ◽  
Aβ Peptides

Discovery and development of clinically useful biomarkers for Alzheimer’s disease (AD) and related dementias have been the focus of recent research efforts. While cerebrospinal fluid and positron emission tomography or MRI-based neuroimaging markers have made the in vivo detection of AD pathology and its consequences possible, the high cost and invasiveness have limited their widespread use in the clinical setting. On the other hand, advances in potentially more accessible blood-based biomarkers had been impeded by lack of sensitivity in detecting changes in markers of the hallmarks of AD, including amyloid-β (Aβ) peptides and phosphorylated tau (P-tau). More recently, however, emerging technologies with superior sensitivity and specificity for measuring Aβ and P-tau have reported high concordances with AD severity. In this focused review, we describe several emerging technologies, including immunoprecipitation-mass spectrometry (IP-MS), single molecule array and Meso Scale Discovery immunoassay platforms, and appraise the current literature arising from their use to identify plaques, tangles and other AD-associated pathology. While there is potential clinical utility in adopting these technologies, we also highlight the further studies needed to establish Aβ and P-tau as blood-based biomarkers for AD, including validation with existing large sample sets, new independent cohorts from diverse backgrounds as well as population-based longitudinal studies. In conclusion, the availability of sensitive and reliable measurements of Aβ peptides and P-tau species in blood holds promise for the diagnosis, prognosis and outcome assessments in clinical trials for AD.

Cognitive enhancement of volatile oil from the stems of Schisandra chinensis Baill. in Alzheimer’s disease rats

2018 ◽  
Vol 96 (6) ◽  
pp. 550-555 ◽  
Author(s):  
Bingyou Yang ◽  
Bo Liu ◽  
Yan Liu ◽  
Hua Han ◽  
Haixue Kuang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Deficits ◽  
Amyloid Β ◽  
Volatile Oil ◽  
Gas Chromatography Mass Spectrometry ◽  
Morris Water Maze Test ◽  
Schisandra Chinensis ◽  
Nerve Growth ◽  
Necrosis Factor

The volatile oil (VO), extracted from the stems of Schisandra chinensis Baill. (SCS), was separated and identified by gas chromatography – mass spectrometry. The study was devised to investigate the effects of VO on oxidative stress and cognitive deficits induced by amyloid-β (Aβ(1-42)). Alzheimer’s disease (AD) models were established by injecting Aβ(1-42) into the rat hippocampus and the effects of learning and memory were observed by a Morris water maze test, immunohistological alterations, and correlative indicators covering nerve growth (brain-derived neurotrophic factor, glial-cell-derived trophic factor, and nerve growth factor), interleukin 1β, tumor necrosis factor, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), glial fibrillary acidic protein (GFAP), and microglial CD11b in AD rats. And activities of SOD, MDA, and GSH-Px were ameliorated by VO. The neurotrophic factors GFAP and microglial CD11b were noticeably improved in histopathologic changes. These data suggested that VO from SCS had potential activities for the prevention and treatment of AD.

scholarly journals Vitamin A and vitamin E metabolites comodulate amyloid-β aggregation

2021 ◽  
Author(s):  
Priyanka Joshi ◽  
Sean Chia ◽  
Xiaoting Yang ◽  
Michele Perni ◽  
Johnny Habchi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vitamin E ◽  
Vitamin A ◽  
Protein Aggregation ◽  
Amyloid Β ◽  
Water Soluble ◽  
Alpha Tocopherol ◽  
Cellular Environment ◽  
Model Of Alzheimer’S Disease

Alzheimer's disease is characterized by the presence in the brain of amyloid plaques formed by the aberrant deposition of the amyloid-beta; peptide (Abeta). Since many vitamins are dysregulated in this disease, we explored whether these molecules participate in protein homeostasis by modulating Abeta; aggregation. By screening 18 fat-soluble and water-soluble vitamins, we found that retinoic acid and alpha-tocopherol, two metabolites of vitamin A and vitamin E, respectively, affect Abeta; aggregation both in vitro and in a C. elegans model of Alzheimer's disease. We also show that effects of these two vitamin metabolites in combination can cancel each other out, suggesting that the complex composition of the cellular environment could have a protective role against protein aggregation through the simultaneous presence of aggregation promoters and inhibitors. Taken together, these results indicate that vitamins and their metabolites may be added to the list of components of the quality control system that regulate protein aggregation.

Single-Molecule Imaging of Amyloid-β Protein (Aβ) of Alzheimer’s Disease

2014 ◽  
pp. 47-56
Author(s):  
Marie-Isabel Aguilar ◽  
Xu Hou ◽  
Dusan Losic ◽  
Adam I. Mechler ◽  
Lisandra L. Martin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Single Molecule ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Single Molecule Imaging ◽  
Β Protein

Target Enzyme in Alzheimer’s Disease: Acetylcholinesterase Inhibitors

2019 ◽  
Vol 19 (4) ◽  
pp. 264-275 ◽  
Author(s):  
Mridula Saxena ◽  
Ragini Dubey
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Single Molecule ◽  
Rational Design ◽  
Large Population ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Amyloid Β ◽  
Learning Ability ◽  
Hybrid Molecules

Alzheimer’s Disease (AD), affecting a large population worldwide is characterized by the loss of memory and learning ability in the old population. The enzyme Acetylcholinesterase Enzyme (AChE) is the key enzyme in the hydrolysis of the neurotransmitter acetylcholine and is also the target of most of the clinically used drugs for the treatment of AD but these drugs provide only symptomatic treatment and have the limitation of loss of therapeutic efficacy with time. The development of different strategies targeting the AChE enzyme along with other targets like Butyl Cholinesterase (BChE), amyloid-β (Aβ), β-secretase-1 (BACE), metals antioxidant properties and free radical scavenging capacity has been focused in recent years. Literature search was conducted for the molecules and their rational design which have shown inhibition for AChE and the other abovementioned targets. Several hybrid molecules incorporating the main sub-structures derived from diverse chemotypes like acridine, quinoline, carbamates, and other heterocyclic analogs have shown desired pharmacological activity with a good profile in a single molecule. It is followed by optimization of the activity through structural modifications guided by structure-activity relationship studies. It has led to the discovery of novel molecules 17b, 20, and 23 with desired AChE inhibition along with desirable activity against other abovementioned targets for further pre-clinical studies.

scholarly journals Human iPSC-derived astrocytes transplanted into the mouse brain display three morphological responses to amyloid-β plaques

2020 ◽  
Author(s):  
Pranav Preman ◽  
Julia TCW ◽  
Sara Calafate ◽  
An Snellinx ◽  
Maria Alfonso-Triguero ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Brain ◽  
Morphological Changes ◽  
Amyloid Β ◽  
Induced Pluripotent Stem Cell ◽  
Immunodeficient Mice ◽  
A Cell ◽  
Induced Pluripotent ◽  
Chimeric Model

ABSTRACTBackgroundIncreasing evidence for a direct contribution of astrocytes to neuroinflammatory and neurodegenerative processes causing Alzheimer’s disease comes from molecular studies in rodent models. However, these models may not fully recapitulate human disease as human and rodent astrocytes differ considerably in morphology, functionality, and gene expression.MethodsTo address these challenges, we established an approach to study human astroglia within the context of the mouse brain by transplanting human induced pluripotent stem cell (hiPSC)-derived glia progenitors into neonatal brains of immunodeficient mice.ResultsXenografted (hiPSC)-derived glia progenitors differentiate into astrocytes that integrate functionally within the mouse host brain and mature in a cell-autonomous way retaining human-specific morphologies, unique features and physiological properties. In Alzheimer’s chimeric brains, transplanted hiPSC-derived astrocytes respond to the presence of amyloid plaques with various morphological changes that seem independent of the APOE allelic background.ConclusionIn sum, this chimeric model has great potential to analyze the role of patient-derived and genetically modified astroglia in Alzheimer’s disease.

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