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https://www.readbyqxmd.com/read/28922846/different-complicated-brain-pathologies-in-monozygotic-twins-with-gerstmann-str%C3%A3-ussler-scheinker-disease
#1
Hiroyuki Honda, Kensuke Sasaki, Hiroshi Takashima, Daisuke Mori, Sachiko Koyama, Satoshi O Suzuki, Toru Iwaki
Gerstmann-Sträussler-Scheinker disease (GSS) is an autosomal, dominantly inherited prion disease. In this study, we present different complicated brain pathologies determined postmortem of monozygotic GSS twin sisters. Case 1 showed cerebellar ataxia at the age of 58 years, and died at 66 years. Case 2 became symptomatic at the age of 75 years, and died at 79 years. There was a 17-year difference in the age of onset between the twins. Postmortem examination revealed numerous prion protein (PrP) plaques in the brains of both cases...
October 1, 2017: Journal of Neuropathology and Experimental Neurology
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
#2
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/28922400/protein-folding-misfolding-and-aggregation-the-importance-of-two-electron-stabilizing-interactions
#3
Andrzej Stanisław Cieplak
Proteins associated with neurodegenerative diseases are highly pleiomorphic and may adopt an all-α-helical fold in one environment, assemble into all-β-sheet or collapse into a coil in another, and rapidly polymerize in yet another one via divergent aggregation pathways that yield broad diversity of aggregates' morphology. A thorough understanding of this behaviour may be necessary to develop a treatment for Alzheimer's and related disorders. Unfortunately, our present comprehension of folding and misfolding is limited for want of a physicochemical theory of protein secondary and tertiary structure...
2017: PloS One
https://www.readbyqxmd.com/read/28922344/comparison-table-drugs-for-alzheimer-s-disease
#4
(no author information available yet)
No abstract text is available yet for this article.
September 25, 2017: Medical Letter on Drugs and Therapeutics
https://www.readbyqxmd.com/read/28922162/sphingolipids-in-alzheimer-s-disease-and-related-disorders
#5
Pilar Martinez Martinez, Michelle Mielke
No abstract text is available yet for this article.
September 11, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28922161/comorbidity-analysis-between-alzheimer-s-disease-and-type-2-diabetes-mellitus-t2dm-based-on-shared-pathways-and-the-role-of-t2dm-drugs
#6
Reagon Karki, Alpha Tom Kodamullil, Martin Hofmann-Apitius
BACKGROUND: Various studies suggest a comorbid association between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) indicating that there could be shared underlying pathophysiological mechanisms. OBJECTIVE: This study aims to systematically model relevant knowledge at the molecular level to find a mechanistic rationale explaining the existing comorbid association between AD and T2DM. METHOD: We have used a knowledge-based modeling approach to build two network models for AD and T2DM using Biological Expression Language (BEL), which is capable of capturing and representing causal and correlative relationships at both molecular and clinical levels from various knowledge resources...
September 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28922160/memantine-for-alzheimer-s-disease-an%C3%A2-updated-systematic-review-and%C3%A2-meta-analysis
#7
Taro Kishi, Shinji Matsunaga, Kazuto Oya, Ikuo Nomura, Toshikazu Ikuta, Nakao Iwata
BACKGROUND: The clinical benefit of memantine for Alzheimer's disease (AD) remains inconclusive. OBJECTIVE: We performed an updated systematic review and meta-analysis of the efficacy/safety of memantine in AD. METHODS: We included randomized trials of memantine for AD patients. Cognitive function scores (CF), behavioral disturbances scores (BD), and all-cause discontinuation were used as primary measures. Effect size based on a random-effects model was evaluated in the meta-analyses...
September 11, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28922159/can-musical-or-painting-interventions-improve-chronic-pain-mood-quality-of-life-and-cognition-in-patients-with-mild-alzheimer-s-disease-evidence-from-a-randomized-controlled-trial
#8
Elodie Pongan, Barbara Tillmann, Yohana Leveque, Béatrice Trombert, Jean Claude Getenet, Nicolas Auguste, Virginie Dauphinot, Hanane El Haouari, Malou Navez, Jean-Michel Dorey, Pierre Krolak-Salmon, Bernard Laurent, Isabelle Rouch
BACKGROUND: Among non-pharmacological therapies, musical intervention is often used for patients with Alzheimer's disease (AD) and patients presenting with chronic pain. However, their efficacy is still under debate. OBJECTIVE: Our aim was to determine the efficacy of choral singing versus painting sessions on chronic pain, mood, quality of life, and cognition in AD patients. METHODS: In this multicenter randomized controlled trial, 59 mild AD patients were randomized to a 12-week singing (SG; n = 31) or painting group (PG; n = 28)...
September 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28922157/longer-term-investigation-of-the-value-of-18f-fdg-pet-and-magnetic-resonance-imaging-for-predicting-the-conversion-of-mild-cognitive-impairment-to-alzheimer-s-disease-a-multicenter-study
#9
Yoshitaka Inui, Kengo Ito, Takashi Kato
BACKGROUND: The value of fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) and magnetic resonance imaging (MRI) for predicting conversion of mild cognitive impairment (MCI) to Alzheimer's disease (AD) in longer-term is unclear. OBJECTIVE: To evaluate longer-term prediction of MCI to AD conversion using 18F-FDG-PET and MRI in a multicenter study. METHODS: One-hundred and fourteen patients with MCI were followed for 5 years...
September 11, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28922156/soluble-oligomers-require-a-ganglioside-to-trigger-neuronal-calcium-overload
#10
Roberta Cascella, Elisa Evangelisti, Alessandra Bigi, Matteo Becatti, Claudia Fiorillo, Massimo Stefani, Fabrizio Chiti, Cristina Cecchi
An altered distribution of membrane gangliosides (GM), including GM1, has recently been reported in the brains of Alzheimer's disease (AD) patients. Moreover, amyloid-positive synaptosomes obtained from AD brains were found to contain high-density GM1 clusters, suggesting a pathological significance of GM1 increase at presynaptic neuritic terminals in AD. Here, we show that membrane GM1 specifically recruits small soluble oligomers of the 42-residue form of amyloid-β peptide (Aβ42), with intracellular flux of Ca2+ ions in primary rat hippocampal neurons and in human neuroblastoma cells...
September 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28922155/phospho-tau-accumulation-and-structural-alterations-of-the-golgi-apparatus-of-cortical-pyramidal-neurons-in-the-p301s%C3%A2-tauopathy-mouse-model
#11
Alejandro Antón-Fernández, Jesús Merchán-Rubira, Jesús Avila, Félix Hernández, Javier DeFelipe, Alberto Muñoz
The Golgi apparatus (GA) is a highly dynamic organelle involved in the processing and sorting of cellular proteins. In Alzheimer's disease (AD), it has been shown to decrease in size and become fragmented in neocortical and hippocampal neuronal subpopulations. This fragmentation and decrease in size of the GA in AD has been related to the accumulation of hyperphosphorylated tau. However, the involvement of other pathological factors associated with the course of the disease, such as the extracellular accumulation of amyloid-β (Aβ) aggregates, cannot be ruled out, since both pathologies are present in AD patients...
September 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28922154/atrial-fibrillation-is-independently-associated-with-cognitive-impairment-after-ischemic-stroke
#12
Russell Jude Chander, Levinia Lim, Sagarika Handa, Shaun Hiu, Angeline Choong, Xuling Lin, Rajinder Singh, Daniel Oh, Nagaendran Kandiah
BACKGROUND: While atrial fibrillation (AF) is an important risk factor for ischemic strokes and mild cognitive impairment (MCI) in Alzheimer's disease, the association between AF and post-stroke cognitive impairment (PSCI), and the factors mediating this association, is unclear. OBJECTIVE: To investigate the role of AF in PSCI, especially in relation to other markers of cerebrovascular disease. METHODS: 445 subjects with mild ischemic stroke without pre-stroke cognitive decline were assessed 3-6 months post-stroke for cognitive deficits...
September 7, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28922153/sex-dependent-associations-of-serum-uric-acid-with-brain-function-during-aging
#13
Alexandra M Kueider, Yang An, Toshiko Tanaka, Melissa H Kitner-Triolo, Stephanie Studenski, Luigi Ferrucci, Madhav Thambisetty
Serum uric acid (SUA) is an abundant natural antioxidant which could reduce the burden of cellular oxidation, a major cause of neurodegenerative disease. In line with this, SUA levels are lower in those with Alzheimer's disease; however, the association between SUA and cognition remains unclear. Results from studies examining the effects of SUA on cognition may be difficult to interpret in the context of normal versus pathological aging. This study examined sex-specific associations of baseline SUA with cognition during aging...
September 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28922152/brain-biomarkers-in-familial-alzheimer-s-disease-mouse-models
#14
Yafit Kuttner-Hirshler, Palamadai N Venkatasubramanian, Joan Apolinario, Jacqueline Bonds, Alice M Wyrwicz, Orly Lazarov
Alzheimer's disease (AD) is characterized by progressive loss of memory and cognitive deterioration. It is thought that the onset of the disease takes place several decades before memory deficits are apparent. Reliable biomarkers for the diagnosis or prognostication of the disease are highly desirable. Neural stem cells (NSC) exist in the adult brain throughout life and give rise to neural progenitor cells (NPC), which differentiate into neurons or glia. The level of NPC proliferation and new neuron formation is significantly compromised in mouse models of familial Alzheimer's disease (FAD)...
September 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28922151/dickkopf-3-dkk3-improves-amyloid-%C3%AE-pathology-cognitive-dysfunction-and-cerebral-glucose-metabolism-in-a-transgenic-mouse-model-of-alzheimer-s-disease
#15
Li Zhang, Caixian Sun, Yaxi Jin, Kai Gao, Xudong Shi, Wenying Qiu, Chao Ma, Lianfeng Zhang
Dysfunctional Wnt signaling is associated with Alzheimer's disease (AD), and activation of the Wnt signaling pathway inhibits AD development. Dickkopf 3 (Dkk3) is a modulator of the Wnt signaling pathway and is physiologically expressed in the brain. The role of Dkk3 in the pathogenesis of AD has not been evaluated. In the present study, we determined that Dkk3 expression was significantly decreased in brain tissue from AD patients and the AD transgenic mouse model APPswe/PS1dE9 (AD mice). Transgenic mice with brain tissue-specific Dkk3 expression were generated or crossed with AD mice to study the effects of Dkk3 on AD...
September 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28922150/synthesis-radiosynthesis-and-preliminary-in-vitro-and-in-vivo-evaluation-of-the-fluorinated-ceramide-trafficking-inhibitor-hpa-12-for-brain-applications
#16
Simone M Crivelli, Andreas Paulus, Jozef Markus, Matthias Bauwens, Dusan Berkes, Helga E De Vries, Monique T Mulder, Jochen Walter, Felix M Mottaghy, Mario Losen, Pilar Martinez-Martinez
Ceramide levels are increased in blood and brain tissue of Alzheimer's disease (AD) patients. Since the ceramide transporter protein (CERT) is the only known protein able to mediate non-vesicular transfer of ceramide between organelle membranes, the modulation of CERT function may impact on ceramide accumulation. The competitive CERT inhibitor N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl) dodecanamide (HPA-12) interferes with ceramide trafficking. To understand the role of ceramide/CERT in AD, HPA-12 can be a useful tool to modulate ceramide trafficking...
September 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28922067/conceptual-elaboration-versus-direct-lexical-access-in-wais-similarities-differential-effects-of-white-matter-lesions-and-gray-matter-volumes
#17
Sven-Erik Fernaeus, Åke Hellström
Wechsler Adult Intelligence Scale (WAIS) subscale Similarities have been classified as a test of either verbal comprehension or of inductive reasoning. The reason may be that items divide into two categories. We tested the hypothesis of heterogeneity of items in WAIS-Similarities. Consecutive patients at a memory clinic and healthy controls participated in the study. White-matter hyperintensities (WMHs) and normalized temporal lobe volumes were measured based on Magnetic resonance Imaging (MRI), and tests of verbal memory and attention were used in addition to WAIS-Similarities to collect behavioural data...
September 18, 2017: Neuropsychology, Development, and Cognition. Section B, Aging, Neuropsychology and Cognition
https://www.readbyqxmd.com/read/28921979/design-syntheses-and-in-vitro-evaluation-of-new-fluorine-18-radiolabeled-tau-labeling-molecular-probes
#18
Luka Rejc, Lojze Šmid, Vladimir Kepe, Črtomir Podlipnik, Amalija Golobič, Mara Bresjanac, Jorge R Barrio, Andrej Petrič, Janez Košmrlj
Deposition of aggregates of hyperphosphorylated tau protein is a hallmark of tauopathies like Alzheimer and many other neurodegenerative diseases. A sensitive and selective method of in vivo detection of tau-aggregate presence and distribution could provide the means of an early diagnosis of tau-associated diseases. Furthermore, the use of selective molecular probes that enable histochemical differentiation of protein aggregates post mortem would be advantageous for the insight into the properties of tau protein aggregates...
September 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28921611/dendritic-spines-provide-cognitive-resilience-against-alzheimer-s-disease
#19
Benjamin D Boros, Kelsey M Greathouse, Erik G Gentry, Kendall A Curtis, Elizabeth L Birchall, Marla Gearing, Jeremy H Herskowitz
OBJECTIVE: Neuroimaging and other biomarker assays suggest that the pathological processes of Alzheimer's disease (AD) initiate years prior to clinical dementia onset. However some 30%-50% of older individuals that harbor AD pathology do not become symptomatic in their lifetime. It is hypothesized that such individuals exhibit cognitive resilience that protects against AD dementia. We hypothesized that in cases with AD pathology structural changes in dendritic spines would distinguish individuals that had or did not have clinical dementia...
September 16, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28921447/structure-pharmacology-and-roles-in-physiology-of-the-p2y12-receptor
#20
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
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