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alzheimers prevention

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https://www.readbyqxmd.com/read/28922421/effects-of-acute-administration-of-donepezil-or-memantine-on-sleep-deprivation-induced-spatial-memory-deficit-in-young-and-aged-non-human-primate-grey-mouse-lemurs-microcebus-murinus
#1
Anisur Rahman, Yves Lamberty, Esther Schenker, Massimo Cella, Solène Languille, Régis Bordet, Jill Richardson, Fabien Pifferi, Fabienne Aujard
The development of novel therapeutics to prevent cognitive decline of Alzheimer's disease (AD) is facing paramount difficulties since the translational efficacy of rodent models did not resulted in better clinical results. Currently approved treatments, including the acetylcholinesterase inhibitor donepezil (DON) and the N-methyl-D-aspartate antagonist memantine (MEM) provide marginal therapeutic benefits to AD patients. There is an urgent need to develop a predictive animal model that is phylogenetically proximal to humans to achieve better translation...
2017: PloS One
https://www.readbyqxmd.com/read/28921447/structure-pharmacology-and-roles-in-physiology-of-the-p2y12-receptor
#2
Ivar von Kügelgen
P2Y receptors are G-protein-coupled receptors (GPCRs) for extracellular nucleotides. The platelet ADP-receptor which has been denominated P2Y12 receptor is an important target in pharmacotherapy. The receptor couples to Gαi2 mediating an inhibition of cyclic AMP accumulation and additional downstream events including the activation of phosphatidylinositol-3-kinase and Rap1b proteins. The nucleoside analogue ticagrelor and active metabolites of the thienopyridine compounds ticlopidine, clopidogrel and prasugrel block P2Y12 receptors and, thereby, inhibit ADP-induced platelet aggregation...
September 12, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28920073/design-of-pilot-studies-to-inform-the-construction-of-composite-outcome-measures
#3
Steven D Edland, M Colin Ard, Weiwei Li, Lingjing Jiang
BACKGROUND: Composite scales have recently been proposed as outcome measures for clinical trials. For example, the Prodromal Alzheimer's Cognitive Composite (PACC) is the sum of z-score normed component measures assessing episodic memory, timed executive function, and global cognition. Alternative methods of calculating composite total scores using the weighted sum of the component measures that maximize signal-to-noise of the resulting composite score have been proposed. Optimal weights can be estimated from pilot data, but it is an open question how large a pilot trial is required to calculate reliably optimal weights...
June 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/28919253/the-influence-of-acidic-media-on-the-effect-of-beta-amyloid-peptide-on-the-function-of-glycine-receptor-in-hippocampal-neurons
#4
J V Bukanova, E I Solntseva, R V Kondratenko, V G Skrebitsky
We have previously shown that application of beta-amyloid peptide 1-42 (Aβ) at picomolar/nanomolar concentrations caused a decrease in the peak amplitude and acceleration of desensitization of the glycine-activated chloride current (IGly) in hippocampal pyramidal neurons (Bukanova et al., 2016). The aim of this work was to study the effect of Aβ on IGly in an acidified medium. The relevance of this work is determined by the fact that the pathogenic effects of Aβ in Alzheimer's disease are usually accompanied by inflammatory processes and acidosis...
September 15, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28919107/combination-of-a%C3%AE-suppression-and-innate-immune-activation-in-the-brain-significantly-attenuates-amyloid-plaque-deposition
#5
Christophe Verbeeck, Anna Carrano, Paramita Chakrabarty, Joanna L Jankowsky, Pritam Das
Anti-Aβ clinical trials are currently underway to determine whether preventing amyloid deposition will be beneficial in arresting progression of Alzheimer disease. Both clinical and pre-clinical studies suggest that anti-amyloid strategies are only effective if started at very early stages of the disease process in a primary prevention strategy. Because this approach will be difficult to deploy, strategies for secondary prevention aimed at later stages of disease are also needed. In this study, we asked whether combining innate immune activation in the brain with concurrent Aβ suppression could enhance plaque clearance and improve pathological outcomes in mice with moderate amyloid pathology...
September 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28918941/modulation-of-%C3%AE-and-%C3%AE-secretases-as-early-prevention-against-alzheimer-s-disease
#6
REVIEW
Iryna Voytyuk, Bart De Strooper, Lucía Chávez-Gutiérrez
The genetic evidence implicating amyloid-β in the initial stage of Alzheimer's disease is unequivocal. However, the long biochemical and cellular prodromal phases of the disease suggest that dementia is the result of a series of molecular and cellular cascades whose nature and connections remain unknown. Therefore, it is unlikely that treatments directed at amyloid-β will have major clinical effects in the later stages of the disease. We discuss the two major candidate therapeutic targets to lower amyloid-β in a preventive mode, i...
August 10, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28917840/both-nitric-oxide-and-nitrite-prevent-homocysteine-induced-endoplasmic-reticulum-stress-and-subsequent-apoptosis-via-cgmp-dependent-pathway-in-neuronal-cells
#7
Sun-Oh Jeong, Yong Son, Ju Hwan Lee, Seung Won Choi, Sung Hun Kim, Yong-Kwan Cheong, Hun-Taeg Chung, Hyun-Ock Pae
Growing evidence indicates that endoplasmic reticulum (ER) stress and/or ER stress-mediated apoptosis may play a role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease. The present study investigated the effects of non-cytotoxic concentrations of nitric oxide (NO) and nitrite, a metabolite of NO, on ER stress and ER stress-mediated apoptosis in Neuro-2a cells exposed to homocysteine (Hcy), an endogenous ER stress inducer. Hcy induced ER stress, as confirmed by inositol-requiring enzyme 1α (IRE1α) phosphorylation and X-box-binding protein-1 (Xbp1) mRNA splicing as well as C/EBP homologous protein (CHOP) expression, and apoptosis, as verified by Annexin V-positive cells...
September 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28917669/knowledge-driven-computational-modeling-in-alzheimer-s-research-current-state-and-future-trends
#8
Hugo Geerts, Martin Hofmann-Apitius, Thomas J Anastasio
Neurodegenerative diseases such as Alzheimer's disease (AD) follow a slowly progressing dysfunctional trajectory, with a large presymptomatic component and many comorbidities. Using preclinical models and large-scale omics studies ranging from genetics to imaging, a large number of processes that might be involved in AD pathology at different stages and levels have been identified. The sheer number of putative hypotheses makes it almost impossible to estimate their contribution to the clinical outcome and to develop a comprehensive view on the pathological processes driving the clinical phenotype...
September 14, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28916386/molecular-mechanisms-of-the-r61t-mutation-in-apolipoprotein-e4-a-dynamic-rescue
#9
Benfeard Williams, Marino Convertino, Jhuma Das, Nikolay V Dokholyan
The apolipoprotein E4 (ApoE4) gene is the strongest genetic risk factor for Alzheimer's disease (AD). With respect to the other common isoforms of this protein (ApoE2 and ApoE3), ApoE4 is characterized by lower stability that underlies the formation of a stable interaction between the protein's N- and C-terminal domains. AD-related cellular dysfunctions have been linked to this ApoE4 misfolded state. In this regard, it has been reported that the mutation R61T is able to rescue the deleterious cellular effects of ApoE4 by preventing the formation of the misfolded intermediate state...
September 12, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28915562/detecting-the-genetic-link-between-alzheimer-s-disease-and-obesity-using-bioinformatics-analysis-of-gwas-data
#10
Qi-Shuai Zhuang, Hao Zheng, Xiao-Dan Gu, Liang Shen, Hong-Fang Ji
Alzheimer's disease (AD) represents the major form of dementia in the elderly. In recent years, accumulating evidence indicate that obesity may act as a risk factor for AD, while the genetic link between the two conditions remains unclear. This bioinformatics analysis aimed to detect the genetic link between AD and obesity on single nucleotide polymorphisms (SNPs), gene, and pathway levels based on genome-wide association studies data. A total of 31 SNPs were found to be shared by AD and obesity, which were linked to 7 genes...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28911966/fluoxetine-administration-during-adolescence-attenuates-cognitive-and-synaptic-deficits-in-adult-3%C3%A3-tgad-mice
#11
Dong-Sheng Sun, Li-Feng Gao, Li Jin, Hao Wu, Qun Wang, You Zhou, Shuhao Fan, Xia Jiang, Dan Ke, Hao Lei, Jian-Zhi Wang, Gong-Ping Liu
Fluoxetine (FLX) has broad neurobiological functions and neuroprotective effects; however, the preventive effects of FLX on cognitive impairments in Alzheimer's disease (AD) have not been reported. Here, we studied whether adolescent administration of fluoxetine can prevent memory deficits in AD transgenic mice that harbour PS1m146v, APPswe and TauP301L mutations (3 × TgAD). FLX was applied through peritoneal injection to the mice at postnatal day 35 (p35) for 15 consecutive days, and the effects of FLX were observed at 6-month...
September 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28910193/lifestyle-markers-predict-cognitive-function
#12
Steven C Masley, Richard Roetzheim, Gwendolyn Clayton, Angela Presby, Kelley Sundberg, Lucas V Masley
OBJECTIVE: Rates of mild cognitive impairment and Alzheimer's disease are increasing rapidly. None of the current treatment regimens for Alzheimer's disease are effective in arresting progression. Lifestyle choices may prevent cognitive decline. This study aims to clarify which factors best predict cognitive function. METHODS: This was a prospective cross-sectional analysis of 799 men and women undergoing health and cognitive testing every 1 to 3 years at an outpatient center...
September 14, 2017: Journal of the American College of Nutrition
https://www.readbyqxmd.com/read/28910085/cholesterol-changes-the-mechanism-of-a%C3%AE-peptide-binding-to-the-dmpc-bilayer
#13
Christopher Lockhart, Dmitri K Klimov
Using isobaric-isothermal all-atom replica-exchange molecular dynamics (REMD) simulations, we investigated the equilibrium binding of Abeta10-40 monomers to the zwitterionic dimyristoylphosphatidylcholine (DMPC) bilayer containing cholesterol. Our previous REMD simulations, which studied binding of the same peptide to the cholesterol-free DMPC bilayer, served as a control, against which we measured the impact of cholesterol. Our findings are as follows. First, addition of cholesterol to the DMPC bilayer partially expels the Abeta peptide from the hydrophobic core and promotes its binding to bilayer polar headgroups...
September 14, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28906270/microbiota-and-neurodegenerative-diseases
#14
Moira Marizzoni, Stefania Provasi, Annamaria Cattaneo, Giovanni B Frisoni
PURPOSE OF REVIEW: Despite the extensive research carried out in the past decades, the current pathophysiological notions of neurodegenerative disease as well as effective treatments to reduce their progression are largely unknown. Alterations of the human microbiota, the plethora of different microscopic organisms that our body hosts, have been linked to neurodegenerative disease risk, onset and progression. This review summarizes the current knowledge on the possible role of microbiota in neurodegenerative disorders and briefly discusses strategies to restore microbiota homeostasis...
September 12, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28901384/aminoguanidine-exhibits-an-inhibitory-effect-on-%C3%AE-%C3%A2-amyloid%C3%A2-induced-damage-in-f98-glioma-cells
#15
Tao Chen, Xiao-Li Sun, Xi-Ai Yang, Jing-Jing Shi, Yi Liu, Jia-Ming Gong
The present study investigated the role of aminoguanidine in the prevention of harmful effects in astroglioma F98 cells induced by β‑amyloid treatment. MTT assay was used to analyze cell viability. Expression of inducible nitric oxide synthase (iNOS) was analyzed using western blot analysis. Treatment of the F98 cells with a 15 µM concentration of β‑amyloid for 12 h reduced cell viability to 18% compared with the control cells. However, pretreatment with a 30 µM concentration of aminoguanidine for 12 h completely prevented the β‑amyloid‑induced reduction in cell viability...
August 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28900376/physical-activity-and-beta-amyloid-pathology-in-alzheimer-s-disease-a-sound-mind-in-a-sound-body
#16
REVIEW
Khadije Ebrahimi, Alireza Majdi, Behrouz Baghaiee, Seyed Hojjat Hosseini, Saeed Sadigh-Eteghad
Alzheimer's disease (AD) is the most common type of dementia worldwide. Since curative treatment has not been established for AD yet and due to heavy financial and psychological costs of patients' care, special attention has been paid to preventive interventions such as physical activity. Evidence shows that physical activity has protective effects on cognitive function and memory in AD patients. Several pathologic factors are involved in AD-associated cognitive impairment some of which are preventable by physical activity...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28900242/dietary-docosahexaenoic-acid-dha-as-lysophosphatidylcholine-but-not-as-free-acid-enriches-brain-dha-and-improves-memory-in-adult-mice
#17
Dhavamani Sugasini, Riya Thomas, Poorna C R Yalagala, Leon M Tai, Papasani V Subbaiah
Docosahexaenoic acid (DHA) is uniquely concentrated in the brain, and is essential for its function, but must be mostly acquired from diet. Most of the current supplements of DHA, including fish oil and krill oil, do not significantly increase brain DHA, because they are hydrolyzed to free DHA and are absorbed as triacylglycerol, whereas the transporter at blood brain barrier is specific for phospholipid form of DHA. Here we show that oral administration of DHA to normal adult mice as lysophosphatidylcholine (LPC) (40 mg DHA/kg) for 30 days increased DHA content of the brain by >2-fold...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28900205/apoe4-associated-phospholipid-dysregulation-contributes-to-development-of-tau-hyper-phosphorylation-after-traumatic-brain-injury
#18
Jiqing Cao, Farida El Gaamouch, James S Meabon, Kole D Meeker, Li Zhu, Margaret B Zhong, John Bendik, Gregory Elder, Ping Jing, Jiahong Xia, Wenjie Luo, David G Cook, Dongming Cai
The apolipoprotein E4 (ApoE4) genotype combines with traumatic brain injury (TBI) to increase the risk of developing Alzheimer's Disease (AD). However, the underlying mechanism(s) is not well-understood. We found that after exposure to repetitive blast-induced TBI, phosphoinositol biphosphate (PIP2) levels in hippocampal regions of young ApoE3 mice were elevated and associated with reduction in expression of a PIP2 degrading enzyme, synaptojanin 1 (synj1). In contrast, hippocampal PIP2 levels in ApoE4 mice did not increase after blast TBI...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28900185/anti-a%C3%AE-single-chain-variable-fragment-antibodies-restore-memory-acquisition-in-a-drosophila-model-of-alzheimer-s-disease
#19
Alfonso Martin-Peña, Diego E Rincon-Limas, Pedro Fernandez-Funez
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder triggered by the accumulation of soluble assemblies of the amyloid-β42 (Aβ42) peptide. Despite remarkable advances in understanding the pathogenesis of AD, the development of palliative therapies is still lacking. Engineered anti-Aβ42 antibodies are a promising strategy to stall the progression of the disease. Single-chain variable fragment (scFv) antibodies increase brain penetration and offer flexible options for delivery while maintaining the epitope targeting of full antibodies...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28899450/joining-forces-to-prevent-dementia-the-international-research-network-on-dementia-prevention-irndp
#20
Kaarin J Anstey, Ruth Peters, Linda Clare, Nicola T Lautenschlager, Hiroko H Dodge, Deborah E Barnes, Suzana Shahar, Henry Brodaty, Glenn Rees
Dementia is a neurodegenerative disorder with global impact, with the largest proportion of cases occurring in low- and middle-income countries. It is estimated that there are 46.8 million cases globally with approximately 10 million new cases each year or a new case occurring every 3 sec (Prince et al., 2015). For comparison there are 36.7 million HIV cases with an estimated 2 million new cases each year (WHO, 2017). The rise in dementia prevalence is largely due to population ageing, with the oldest being at highest risk...
September 13, 2017: International Psychogeriatrics
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