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https://www.readbyqxmd.com/read/28918286/identifying-combinatorial-biomarkers-by-association-rule-mining-in-the-camd-alzheimer-s-database
#1
Balázs Szalkai, Vince K Grolmusz, Vince I Grolmusz
The concept of combinatorial biomarkers was conceived when it was noticed that simple biomarkers are often inadequate for recognizing and characterizing complex diseases. Here we present an algorithmic search method for complex biomarkers which may predict or indicate Alzheimer's disease (AD) and other kinds of dementia. We show that our method is universal since it can describe any Boolean function for biomarker discovery. We applied data mining techniques that are capable to uncover implication-like logical schemes with detailed quality scoring...
August 17, 2017: Archives of Gerontology and Geriatrics
https://www.readbyqxmd.com/read/28918230/biosensing-methods-for-determination-of-triglycerides-a-review
#2
REVIEW
C S Pundir, Vinay Narwal
Triglycerides (TGs) are the major transporters of dietary fats throughout the bloodstream. Besides transporting fat, TGs also act as stored fat in adipose tissue, which is utilized during insufficient carbohydrates supply. TG level is below 150mg/dL in healthy persons. Elevated TGs level in blood over 500mg/dL is a biomarker for cardiovascular diseases, Alzheimer disease, pancreatitis and diabetes. Numerous methods are accessible for recognition of TGs, among them, most are cumbersome, time-consuming, require sample pre-treatment, high cost instrumental set-up and experienced personnel to operate...
September 9, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28918204/serum-glial-cell-line-derived-neurotrophic-factor-levels-and-postoperative-cognitive-dysfunction-after-surgery-for-rheumatic-heart-disease
#3
Xiaoxia Duan, Tao Zhu, Chan Chen, Guanpeng Zhang, Junhui Zhang, Lin Wang, Luye Zhang, Maohua Wang, Xiaobin Wang
OBJECTIVE: Postoperative cognitive dysfunction is an important complication of cardiac surgery with poor outcomes. Serum glial cell line-derived neurotrophic factor levels are decreased in patients with Alzheimer's disease, but the association between glial cell line-derived neurotrophic factor levels and postoperative cognitive dysfunction is poorly understood. The present study aimed to investigate the prognostic value of postoperative serum glial cell line-derived neurotrophic factor levels to predict postoperative cognitive dysfunction in patients with rheumatic heart disease undergoing heart valve replacement...
August 24, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28918172/melatonin-and-periodontal-tissues-molecular-and-clinical-perspectives
#4
REVIEW
Agata Rita Carpentieri, María Elena Peralta Lopez, Javier Aguilar, Verónica Mariana Solá
Periodontal disease is a frequent chronic inflammatory pathology that implies the destruction of the tissues supporting the teeth, which represents a high sanitary cost. It usually appears associated with other systemic conditions such as diabetes, metabolic syndrome, depression and Alzheimer disease among others. The presence of melatonin and its receptors in the oral cavity supports the hypothesis that this hormone could play a role in homeostasis of periodontal tissues. In the present review we will discuss the potential role of melatonin, a circadian synchronizing hormone, with proved antiinflammatory and antioxidant profile, in the pathogenesis and treatment of periodontitis...
September 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28917980/absence-of-association-of-the-ala58val-rs17571-ctsd-gene-variant-with-parkinson-s-disease-or-amyotrophic-lateral-sclerosis-in-a-han-chinese-population
#5
Jing Xi, Xinglong Yang, Quanzhen Zhao, Jinhua Zheng, Ran An, Sijia Tian, Hongyan Huang, Pingping Ning, Yanming Xu
Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) are neurodegenerative diseases that may share genetic risk factors. The exon variant Aal58Val (rs17571) in CTSD was recently associated with AD, leading us to examine whether it also affects risk of ALS and PD. The rs17571 variant was genotyped using the ligase detection reaction in 569 Han Chinese patients with PD, 301 patients with ALS, and healthy controls age- and gender-matched to each patient group. The frequencies of genotypes and alleles were similar between each disease group and its respective control group...
September 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28917978/sen1500-a-novel-oral-amyloid-%C3%AE-aggregation-inhibitor-attenuates-brain-pathology-in-a-mouse-model-of-alzheimer-s-disease
#6
D Brunner, S Flunkert, J Neddens, S Duller, D I C Scopes, J M Treherne, B Hutter-Paier
INTRODUCTION: Amyloid-β (Aβ) aggregation is thought to be a major pathogenic event underlying the neuropathology of Alzheimer's disease (AD). The development of new drugs inhibiting the Aβ aggregation process is, therefore, important. SEN1500, an orally bioavailable and CNS-penetrant Aβ aggregation inhibitor, has previously been shown to reduce spatial learning and memory deficits in an APP transgenic mouse model. To verify that the pharmacological properties of SEN1500 are not unique to this model, we investigated brain Aβ pathology, neuroinflammation, as well as memory in a different mouse model of AD expressing the human amyloid precursor protein with Swedish and London mutations (APPSL)...
September 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28917942/in-vivo-and-in-vitro-testing-of-native-%C3%AE-conotoxins-from-the-injected-venom-of-conus-purpurascens
#7
REVIEW
Mickelene F Hoggard, Alena M Rodriguez, Herminsul Cano, Evan Clark, Han-Shen Tae, David J Adams, Tanja A Godenschwege, Frank Marí
α-Conotoxins inhibit nicotinic acetylcholine receptors (nAChRs) and are used as probes to study cholinergic pathways in vertebrates. Model organisms, such as Drosophila melanogaster, express nAChRs in their CNS that are suitable to investigate the neuropharmacology of α-conotoxins in vivo. Here we report the paired nanoinjection of native α-conotoxin PIA and two novel α-conotoxins, PIC and PIC[O7], from the injected venom of Conus purpurascens and electrophysiological recordings of their effects on the giant fiber system (GFS) of D...
September 13, 2017: Neuropharmacology
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
#8
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/28917837/memantine-inhibits-%C3%AE-amyloid-aggregation-and-disassembles-preformed-%C3%AE-amyloid-aggregates
#9
Kaori Ito, Mitsuhiro Makino, Keiko Okado, Taisuke Tomita
Memantine, an uncompetitive glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist, is widely used as a medication for the treatment of Alzheimer's disease (AD). We previously reported that chronic treatment of AD with memantine reduces the amount of insoluble β-amyloid (Aβ) and soluble Aβ oligomers in animal models of AD. The mechanisms by which memantine reduces Aβ levels in the brain were evaluated by determining the effect of memantine on Aβ aggregation using thioflavin T and transmission electron microscopy...
September 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28917724/backward-genotype-transcript-phenotype-association-mapping
#10
Seunghak Lee, Haohan Wang, Eric P Xing
Genome-wide association studies have discovered a large number of genetic variants associated with complex diseases such as Alzheimer's disease. However, the genetic background of such diseases is largely unknown due to the complex mechanisms underlying genetic effects on traits, as well as a small sample size (e.g., 1000) and a large number of genetic variants (e.g., 1 million). Fortunately, datasets that contain genotypes, transcripts, and phenotypes are becoming more readily available, creating new opportunities for detecting disease-associated genetic variants...
September 13, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28917669/knowledge-driven-computational-modeling-in-alzheimer-s-research-current-state-and-future-trends
#11
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/28917667/amyloid-%C3%AE-42-clearance-and-neuroprotection-mediated-by-x-box-binding-protein-1-signaling-decline-with-aging-in-the-drosophila-brain
#12
María S Marcora, Lautaro F Belfiori-Carrasco, Nadia I Bocai, Laura Morelli, Eduardo M Castaño
The unfolded protein response (UPR) may be pathogenically related to Alzheimer's disease. Yet, the effects of chronic amyloid-β42 (Aβ42) accumulation and UPR activation upon neurotoxicity remain unclear. Here, we show that neuronal Aβ42 expression in Drosophila activated the inositol-requiring protein-1/X-box binding protein 1 (XBP1) UPR branch before the onset of behavioral impairment and persisted with aging. Early upregulation of hsc3/BiP, a target of XBP1 and activating transcription factor 6 pathways, was also sustained in old animals...
August 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28917260/roles-of-sigma-1-receptors-on-mitochondrial-functions-relevant-to-neurodegenerative-diseases
#13
REVIEW
Tzu-Yu Weng, Shang-Yi Anne Tsai, Tsung-Ping Su
The sigma-1 receptor (Sig-1R) is a chaperone that resides mainly at the mitochondrion-associated endoplasmic reticulum (ER) membrane (called the MAMs) and acts as a dynamic pluripotent modulator in living systems. At the MAM, the Sig-1R is known to play a role in regulating the Ca(2+) signaling between ER and mitochondria and in maintaining the structural integrity of the MAM. The MAM serves as bridges between ER and mitochondria regulating multiple functions such as Ca(2+) transfer, energy exchange, lipid synthesis and transports, and protein folding that are pivotal to cell survival and defense...
September 16, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28916821/reduced-basal-forebrain-atrophy-progression-in-a-randomized-donepezil-trial-in-prodromal-alzheimer-s-disease
#14
Enrica Cavedo, Michel J Grothe, Olivier Colliot, Simone Lista, Marie Chupin, Didier Dormont, Marion Houot, Stephane Lehéricy, Stefan Teipel, Bruno Dubois, Harald Hampel
Acetylcholinesterase inhibitors are approved drugs currently used for the treatment of Alzheimer's disease (AD) dementia. Basal forebrain cholinergic system (BFCS) atrophy is reported to precede both entorhinal cortex atrophy and memory impairment in AD, challenging the traditional model of the temporal sequence of topographical pathology associated with AD. We studied the effect of one-year Donepezil treatment on the rate of BFCS atrophy in prodromal AD patients using a double-blind, randomized, placebo-controlled trial of Donepezil (10 mg/day)...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916627/interactions-between-medial-prefrontal-cortex-and-dorsomedial-striatum-are-necessary-for-odor-span-capacity-in-rats-role-of-glun2b-containing-nmda-receptors
#15
Don A Davies, Quentin Greba, Jantz C Selk, Jillian K Catton, Landon D Baillie, Sean J Mulligan, John G Howland
Working memory is involved in the maintenance and manipulation of information essential for complex cognition. While the neural substrates underlying working memory capacity have been studied in humans, considerably less is known about the circuitry mediating working memory capacity in rodents. Therefore, the present experiments tested the involvement of medial prefrontal cortex (mPFC) and dorsal striatum (STR) in the odor span task (OST), a task proposed to assay working memory capacity in rodents. Initially, Long Evans rats were trained to dig in scented sand for food following a serial delayed nonmatching-to-sample rule...
October 2017: Learning & Memory
https://www.readbyqxmd.com/read/28916532/comparison-of-symptomatic-and-asymptomatic-persons-with-primary-age-related-tauopathy
#16
Lilah M Besser, John F Crary, Charles Mock, Walter A Kukull
OBJECTIVE: To conduct a clinicopathologic study to characterize clinical and neuropathologic features associated with cognitive impairment in participants with no neuritic amyloid plaques (primary age-related tauopathy [PART] definite) and sparse neuritic plaques (amyloid sparse). METHODS: Using the National Alzheimer's Coordinating Center database, we identified 377 individuals who were PART definite (n = 170) or amyloid sparse (n = 207), clinically examined within 1 year of death, and autopsied at 1 of 26 National Institute on Aging-funded Alzheimer's Disease Centers...
September 15, 2017: Neurology
https://www.readbyqxmd.com/read/28916531/diabetes-prediabetes-and-brain-volumes-and-subclinical-cerebrovascular-disease-on-mri-the-atherosclerosis-risk-in-communities-neurocognitive-study-aric-ncs
#17
Andrea L C Schneider, Elizabeth Selvin, A Richey Sharrett, Michael Griswold, Josef Coresh, Clifford R Jack, David Knopman, Thomas Mosley, Rebecca F Gottesman
OBJECTIVE: To examine the associations of prediabetes, diabetes, and diabetes severity (as assessed by HbA1c and diabetes duration) with brain volumes and vascular pathology on brain MRI and to assess whether the associations of diabetes with brain volumes are mediated by brain vascular pathology. RESEARCH DESIGN AND METHODS: Cross-sectional study of 1,713 participants in the Atherosclerosis Risk in Communities Neurocognitive Study (mean age 75 years, 60% female, 27% black, 30% prediabetes, and 35% diabetes) who underwent 3T brain MRI scans in 2011-2013...
September 15, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28916413/emerging-structural-understanding-of-amyloid-fibrils-by-solid-state-nmr
#18
REVIEW
Beat H Meier, Roland Riek, Anja Böckmann
Amyloid structures at atomic resolution have remained elusive mainly because of their extensive polymorphism and because their polymeric properties have hampered structural studies by classical approaches. Progress in sample preparation, as well as solid-state NMR methods, recently enabled the determination of high-resolution 3D structures of fibrils such as the amyloid-β fibril, which is involved in Alzheimer's disease. Notably, the simultaneous but independent structure determination of Aβ1-42, a peptide that forms fibrillar deposits in the brain of Alzheimer patients, by two independent laboratories, which yielded virtually identical results, has highlighted how structures can be obtained that allow further functional investigation...
September 12, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28916386/molecular-mechanisms-of-the-r61t-mutation-in-apolipoprotein-e4-a-dynamic-rescue
#19
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/28916328/primary-hippocampal-neuronal-cell-death-induction-after-acute-and-repeated-paraquat-exposures-mediated-by-ache-variants-alteration-and-cholinergic-and-glutamatergic-transmission-disruption
#20
Javier Del Pino, Paula Moyano, Gloria Gómez Díaz, María José Anadon, Maria Jesus Diaz, José Manuel García, Margarita Lobo, Adela Pelayo, Emma Sola, María Teresa Frejo
Paraquat (PQ) is a widely used non-selective contact herbicide shown to produce memory and learning deficits after acute and repeated exposure similar to those induced in Alzheimer's disease (AD). However, the complete mechanisms through which it induces these effects are unknown. On the other hand, cholinergic and glutamatergic systems, mainly in the hippocampus, are involved on learning, memory and cell viability regulation. An alteration of hippocampal cholinergic or glutamatergic transmissions or neuronal cell loss may induce these effects...
September 12, 2017: Toxicology
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