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https://www.readbyqxmd.com/read/28528321/omega-3-fatty-acids-lipids-and-apoe-lipidation-in-alzheimer-s-disease-a-rationale-for-multi-nutrient-dementia-prevention
#1
Marcus O Grimm, Daniel Michaelson, Tobias Hartmann
In the last decade it has become obvious that Alzheimer's disease (AD) is closely linked to changes in lipids or lipid metabolism. One of the main pathological hallmarks of AD is amyloid-β (Aβ) deposition. Aβ is derived from sequential proteolytic processing of the amyloid precursor protein (APP). Interestingly, both, the APP and all APP secretases are transmembrane proteins which cleave APP close to and in the lipid bilayer. Moreover, apolipoprotein E4 (apoE4) has been identified as the most prevalent genetic risk factor for AD...
May 20, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28528185/simvastatin-ameliorate-memory-deficits-and-inflammation-in-clinical-and-mouse-model-of-alzheimer-s-disease-via-modulating-the-expression-of-mir-106b
#2
Wenzhong Huang, Zhenyu Li, Liandong Zhao, Wei Zhao
BACKGROUND: Alzheimer's disease (AD) as a neurodegenerative brain disorder is a devastating pathology leading to disastrous cognitive impairments and dementia, and several studies have shown that AD is closely related to the inflammation, so anti-inflammatory treatment may provide therapeutic benefits. In this study, the effect of simvastatin on inflammation was investigated and the underlying mechanisms were explored. METHODS: First, we tested the effect of simvastatin on AD in clinical research...
May 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28528007/luteolin-as-a-potential-preventive-and-therapeutic-candidate-for-alzheimer-s-disease
#3
Youngjoo Kwon
Amyloid cascade hypothesis is the main theoretical framework describing the development of Alzheimer's disease (AD). However, most clinical trials of therapy targeting amyloid-β peptide (Aβ) are unsuccessful because AD is a complex disease involving many genetic and environmental factors. Among various factors, inflammation within the brain in particular has been implicated in the pathogenesis and progression of AD. Furthermore, it has been shown that systemic inflammation can initiate AD. Therefore, anti-inflammatory agents might be beneficial for prevention and/or treatment of AD...
May 17, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28527630/diagnostic-accuracy-of-csf-neurofilament-light-chain-protein-in-the-biomarker-guided-classification-system-for-alzheimer-s-disease
#4
Simone Lista, Nicola Toschi, Filippo Baldacci, Henrik Zetterberg, Kaj Blennow, Ingo Kilimann, Stefan J Teipel, Enrica Cavedo, Antonio Melo Dos Santos, Stéphane Epelbaum, Foudil Lamari, Bruno Dubois, Roberto Floris, Francesco Garaci, Harald Hampel
We assessed the diagnostic accuracy of cerebrospinal fluid (CSF) neurofilament light chain (NFL) protein in the classification of patients with Alzheimer's disease (AD) and cognitively healthy control individuals (HCs) and patients with frontotemporal dementia (FTD) as comparisons. Particularly, we tested the performance of CSF NFL concentration in differentiating patient groups stratified by fluid biomarker profiles, independently of the severity of cognitive impairment (mild cognitive impairment (MCI) and AD dementia individuals), using a biomarker-guided descriptive classification system for AD...
May 17, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28526839/fluorescence-correlation-spectroscopy-reveals-a-cooperative-unfolding-of-monomeric-amyloid-%C3%AE-42-with-a-low-gibbs-free-energy
#5
Mario Schneider, Stefan Walta, Chris Cadek, Walter Richtering, Dieter Willbold
The amyloid-beta peptide (Aβ) plays a major role in the progression of Alzheimer's disease. Due to its high toxicity, the 42 amino acid long isoform Aβ42 has become of considerable interest. The Aβ42 monomer is prone to aggregation down to the nanomolar range which makes conventional structural methods such as NMR or X-ray crystallography infeasible. Conformational information, however, will be helpful to understand the different aggregation pathways reported in the literature and will allow to identify potential conditions that favour aggregation-incompetent conformations...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526436/intracranial-il-17a-overexpression-decreases-cerebral-amyloid-angiopathy-by-upregulation-of-abca1-in-an-animal-model-of-alzheimer-s-disease
#6
Junling Yang, Jinghong Kou, Robert Lalonde, Ken-Ichiro Fukuchi
Neuroinflammation is a pervasive feature of Alzheimer's disease (AD) and characterized by activated microglia, increased proinflammatory cytokines and/or infiltrating immune cells. T helper 17 (Th17) cells are found in AD brain parenchyma and interleukin-17A (IL-17A) is identified around deposits of aggregated amyloid β protein (Aβ). However, the role of IL-17A in AD pathogenesis remains elusive. We overexpressed IL-17A in an AD mouse model via recombinant adeno-associated virus serotype 5 (rAAV5)-mediated intracranial gene delivery...
May 16, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28526263/n-stearoyl-l-tyrosine-inhibits-the-cell-senescence-and-apoptosis-induced-by-h2o2-in-hek293-tau-cells-via-the-cb2-receptor
#7
Yue Hu, Kai-Yi Zhou, Ze-Jian Wang, Yang Lu, Ming Yin
Although considerable energy and money have been spent trying to inhibit Aβ production and its related metabolic enzyme activities, there are still no drug treatments available to cure even slow for Alzheimer's disease. Therefore, tau protein has been focused recently as the new target for the treatment of Alzheimer's disease. The transfected human embryonic kidney 293 (HEK 293) cells with or without Tau 411 plasmid were used to evaluate the effect of tau protein on cell viability. H2O2 was added to simulate microenvironment of oxidative stress (OS) during aging...
May 16, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28523793/an-exercise-path-to-preventing-alzheimer-s-disease-an-editorial-highlight-on-exercise-and-bdnf-reduce-ab-production-by-enhancing-%C3%AE-secretase-processing-of-app
#8
EDITORIAL
Elizabeth J Coulson, Perry F Bartlett
Read the highlighted article 'Exercise and BDNF reduce Aβ production by enhancing α-secretase processing of APP' on page doi: 10.1111/jnc.14034.
May 18, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28523718/does-sleep-disturbance-affect-the-amyloid-clearance-mechanisms-in-alzheimer-s-disease
#9
REVIEW
Burak Yulug, Lutfu Hanoglu, Ertugrul Kilic
Sleep is one of the important factors that play a key role in AD pathogenesis. However, it is still unclear whether poor quality sleep may overlap with sleep disturbances in the underlying dysfunctional mechanisms of amyloid beta (Aβ) clearance metabolism. Here, we aimed to evaluate the current evidence on the role of sleep deprivation in amyloid beta (Aβ) clearance metabolism. To that end, we discussed possible mechanisms underlying the bidirectional interaction between the sleep deprivation and amyloid beta (Aβ) clearance pathways...
May 18, 2017: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/28522792/transgenic-autoinhibition-of-p21-activated-kinase-exacerbates-synaptic-impairments-and-fronto-dependent-behavioral-deficits-in-an-animal-model-of-alzheimer-s-disease
#10
Cyril Bories, Dany Arsenault, Myriam Lemire, Cyntia Tremblay, Yves De Koninck, Frédéric Calon
Defects in p21-activated kinase (PAK) lead to dendritic spine abnormalities and are sufficient to cause cognition impairment. The decrease in PAK in the brain of Alzheimer's disease (AD) patients is suspected to underlie synaptic and dendritic disturbances associated with its clinical expression, particularly with symptoms related to frontal cortex dysfunction. To investigate the role of PAK combined with Aβ and tau pathologies (3xTg-AD mice) in the frontal cortex, we generated a transgenic model of AD with a deficit in PAK activity (3xTg-AD-dnPAK mice)...
May 16, 2017: Aging
https://www.readbyqxmd.com/read/28522250/ppargamma-agonists-rescue-increased-phosphorylation-of-fgf14-at-s226-in-the-tg2576-mouse-model-of-alzheimer-s-disease
#11
Wei-Chun J Hsu, Norelle Wildburger, Sigmund J Haidacher, Miroslav N Nenov, Oluwarotimi Folorunso, Aditya K Singh, Brent C Chesson, Whitney F Franklin, Ibdanelo Cortez, Rovshan G Sadygov, Kelly T Dineley, Jai Rudra, Giulio Taglialatela, Cheryl F Lichti, Larry Denner, Fernanda Laezza
BACKGROUND: Cognitive impairment in humans with Alzheimer's disease (AD) and in animal models of Aβ-pathology can be ameliorated by treatments with the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARγ) agonists, such as rosiglitazone (RSG). Previously, we demonstrated that in the Tg2576 animal model of AD, RSG treatment rescued cognitive deficits and reduced aberrant activity of granule neurons in the dentate gyrus (DG), an area critical for memory formation...
May 15, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28520803/multiple-modality-biomarker-prediction-of-cognitive-impairment-in-prospectively-followed-de-novo-parkinson-disease
#12
Chelsea Caspell-Garcia, Tanya Simuni, Duygu Tosun-Turgut, I-Wei Wu, Yu Zhang, Mike Nalls, Andrew Singleton, Leslie A Shaw, Ju-Hee Kang, John Q Trojanowski, Andrew Siderowf, Christopher Coffey, Shirley Lasch, Dag Aarsland, David Burn, Lana M Chahine, Alberto J Espay, Eric D Foster, Keith A Hawkins, Irene Litvan, Irene Richard, Daniel Weintraub
OBJECTIVES: To assess the neurobiological substrate of initial cognitive decline in Parkinson's disease (PD) to inform patient management, clinical trial design, and development of treatments. METHODS: We longitudinally assessed, up to 3 years, 423 newly diagnosed patients with idiopathic PD, untreated at baseline, from 33 international movement disorder centers. Study outcomes were four determinations of cognitive impairment or decline, and biomarker predictors were baseline dopamine transporter (DAT) single photon emission computed tomography (SPECT) scan, structural magnetic resonance imaging (MRI; volume and thickness), diffusion tensor imaging (mean diffusivity and fractional anisotropy), cerebrospinal fluid (CSF; amyloid beta [Aβ], tau and alpha synuclein), and 11 single nucleotide polymorphisms (SNPs) previously associated with PD cognition...
2017: PloS One
https://www.readbyqxmd.com/read/28520784/presynaptic-a%C3%AE-40-prevents-synapse-addition-in-the-adult-drosophila-neuromuscular-junction
#13
Begoña López-Arias, Enrique Turiégano, Ignacio Monedero, Inmaculada Canal, Laura Torroja
Complexity in the processing of the Amyloid Precursor Protein, which generates a mixture of βamyloid peptides, lies beneath the difficulty in understanding the etiology of Alzheimer's disease. Moreover, whether Aβ peptides have any physiological role in neurons is an unresolved question. By expressing single, defined Aβ peptides in Drosophila, specific effects can be discriminated in vivo. Here, we show that in the adult neuromuscular junction (NMJ), presynaptic expression of Aβ40 hinders the synaptic addition that normally occurs in adults, yielding NMJs with an invariable number of active zones at all ages tested...
2017: PloS One
https://www.readbyqxmd.com/read/28520620/-epigallocatechin-3-gallate-ameliorates-memory-impairment-and-rescues-the-abnormal-synaptic-protein-levels-in-the-frontal-cortex-and-hippocampus-in-a-mouse-model-of-alzheimer-s-disease
#14
Yufang Guo, Yan Zhao, Ying Nan, Xiang Wang, Yulong Chen, Shuang Wang
(-)-Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenolic extract in green tea and it has attracted increasing attention for its multiple bioactive effects. However, the mechanisms by which EGCG exerts its neuroprotective actions in Alzheimer's disease (AD) are presently lacking. In the present study, a sporadic AD transgenic mouse model known as senescence-accelerated mouse prone 8 (SAMP8) was used to investigate whether oral administration of EGCG could improve recognition and memory function through reduction of amyloid β (Aβ) and tau hyperphosphorylation...
May 17, 2017: Neuroreport
https://www.readbyqxmd.com/read/28515688/insulin-resistance-as-a-link-between-amyloid-beta-and-tau-pathologies-in-alzheimer-s-disease
#15
Roger J Mullins, Thomas C Diehl, Chee W Chia, Dimitrios Kapogiannis
Current hypotheses and theories regarding the pathogenesis of Alzheimer's disease (AD) heavily implicate brain insulin resistance (IR) as a key factor. Despite the many well-validated metrics for systemic IR, the absence of biomarkers for brain-specific IR represents a translational gap that has hindered its study in living humans. In our lab, we have been working to develop biomarkers that reflect the common mechanisms of brain IR and AD that may be used to follow their engagement by experimental treatments...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28515429/endocytic-uptake-of-monomeric-amyloid-%C3%AE-peptides-is-clathrin-and-dynamin-independent-and-results-in-selective-accumulation-of-a%C3%AE-1-42-compared-to-a%C3%AE-1-40
#16
Emelie Wesén, Gavin D M Jeffries, Maria Matson Dzebo, Elin K Esbjörner
Intraneuronal accumulation of amyloid-β (Aβ) peptides represent an early pathological feature in Alzheimer's disease. We have therefore utilized flow cytometry and confocal microscopy in combination with endocytosis inhibition to explore the internalisation efficiency and uptake mechanisms of Aβ(1-40) and Aβ(1-42) monomers in cultured SH-SY5Y cells. We find that both variants are constitutively internalised via endocytosis and that their uptake is proportional to cellular endocytic rate. Moreover, SH-SY5Y cells internalise consistently twice the amount of Aβ(1-42) compared to Aβ(1-40); an imaging-based quantification showed that cells treated with 1 µM peptide for 8 h contained 800,000 peptides of Aβ(1-42) and 400,000 of Aβ(1-40)...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28515043/brain-perivascular-macrophages-initiate-the-neurovascular-dysfunction-of-alzheimer-a%C3%AE-peptides
#17
Laibaik Park, Ken Uekawa, Lidia Garcia-Bonilla, Kenzo Koizumi, Michelle Murphy, Rose Pitstick, Linda H Younkin, Steven G Younkin, Ping Zhou, Geroge A Carlson, Josef Anrather, Costantino Iadecola
Rationale: Increasing evidence indicates that alterations of the cerebral microcirculation may play a role in Alzheimer's disease (AD), the leading cause of late-life dementia. The amyloid-β peptide (Aβ), a key pathogenic factor in AD, induces profound alterations in neurovascular regulation through the innate immunity receptor CD36, which, in turn, activates a Nox2-containing NADPH oxidase leading to cerebrovascular oxidative stress. Brain perivascular macrophages (PVM) located in the perivascular space, a major site of brain Aβ collection and clearance, are juxtaposed to the wall of intracerebral resistance vessels and are a powerful source of reactive oxygen species (ROS)...
May 17, 2017: Circulation Research
https://www.readbyqxmd.com/read/28514851/blood-brain-barrier-penetrating-biologic-tnf-%C3%AE-inhibitor-for-alzheimer-s-disease
#18
Rudy Chang, Jillian Knox, Jae Chang, Aram Derbedrossian, Vitaly Vasilevko, David Cribbs, Ruben J Boado, William M Pardridge, Rachita Sumbria
OBJECTIVE: Tumor necrosis factor alpha (TNF-α) driven processes are involved at multiple stages of Alzheimer's disease (AD) pathophysiology and disease progression. Biologic TNF-α inhibitors (TNFIs) are the most potent class of TNFIs but cannot be developed for AD since these macromolecules do not cross the blood-brain barrier (BBB). A BBB-penetrating TNFI was engineered by the fusion of the extracellular domain of the type II human TNF receptor (TNFR) to a chimeric monoclonal antibody (MAb) against the mouse transferrin receptor (TfR), designated as the cTfRMAb-TNFR fusion protein...
May 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28514831/hypericum-perforatum-extract-attenuates-behavioral-biochemical-and-neurochemical-abnormalities-in-aluminum-chloride-induced-alzheimer-s-disease-rats
#19
Zheng Cao, Fan Wang, Chunyu Xiu, Jian Zhang, Yanfei Li
Alzheimer's disease (AD) is a progressive and ultimately fatal neurodegenerative diseases. Aluminum, a neurotoxic metal, is considered as the pathological hallmark and contributing factor of AD. Hypericum perforatum extract (HPE) is a neuroprotective agent that can prevent neurodegenerative pathologies through antioxidants, anti-inflammatory and regulating neurotransmitter release in animal model of neuropathy. The present study aimed to identify the potential neuroprotective of HPE on AlCl3-induced AD rats...
May 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28513463/alzheimer-s-disease-against-peptides-products-of-enzymatic-cleavage-app-protein-biological-pathobiological-and-physico-chemical-properties-of-fibrillating-peptides
#20
Małgorzata Marszałek
Various peptides products of enzymatic cleavage of key for Alzheimer's disease Amyloid Precursor Protein (APP) are well known, but still are matter of scientific debate. The Aβ type products are especially challenging for experimental and medical research. This paper outlines several, still poorly known, biological and medical processes such as peptides biology, i.e., formation, biodistribution, translocation, transport and finally removal from brain compartments and body fluids like Intracellular Fluid (ICF), Cerebrospinal Fluid (CSF), Interstitial Fluid (ISF), blood serum or urine...
May 17, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
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