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https://www.readbyqxmd.com/read/28743126/frontal-cortex-and-hippocampal-%C3%AE-secretase-activating-protein-levels-in-prodromal-alzheimer-disease
#1
Sylvia E Perez, Muhammad Nadeem, Michael H Malek-Ahmadi, Bin He, Elliott J Mufson
BACKGROUND: β-Amyloid (Aβ) is the product of concerted cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. However, the molecular mechanisms that regulate this process are not well understood. Recently, evidence was reported that γ-secretase activating protein (GSAP, 16 kDa), derived from a larger precursor protein (98 kDa), plays a role in Aβ metabolism through a mechanism involving its interaction with both γ-secretase and APP. However, a detailed evaluation of GSAP protein levels and their association with clinical and neuropathological variables are lacking during the clinical progression of Alzheimer disease (AD)...
July 26, 2017: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/28743115/cerebrospinal-fluid-levels-of-14-3-3-gamma-what-does-it-tell-us-about-sporadic-creutzfeldt-jakob-disease
#2
Christian Humpel, Thomas Benke
Clinical diagnosis of Creutzfeldt-Jakob disease (CJD) can be supported by the analysis of Tau and 14-3-3 in the cerebrospinal fluid (CSF). In this short report, we report about a retrospective analysis performed on 2,296 routinely collected CSF samples, and 44 samples with a ratio of phosphoTau181/Tau <0.075 were selected. Analysis was performed with a novel 14-3-3 gamma CircuLex Elisa. We show that control levels were around 6,000 AU/mL and samples from Alzheimer patients were not different from those collected from healthy controls...
July 26, 2017: Pharmacology
https://www.readbyqxmd.com/read/28742136/can-a-tablet-based-cancellation-test-identify-cognitive-impairment-in-older-adults
#3
Ya-Huei Wu, Jean-Sébastien Vidal, Jocelyne de Rotrou, Sietske A M Sikkes, Anne-Sophie Rigaud, Matthieu Plichart
BACKGROUND AND OBJECTIVE: There has been a growing interest in using computerized cognitive assessment to detect age-related cognitive disorders. We have developed a tablet-based cancellation test (e-CT), previously shown as a reliable measure of executive functions and free of effect of familiarity with computer-based devices in healthy older adults. This study aimed to investigate the influence of demographics and current daily use of computer-based devices in older adults with Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD)...
2017: PloS One
https://www.readbyqxmd.com/read/28742119/doestrare-a-statistical-test-to-identify-local-enrichments-in-rare-genomic-variants-associated-with-disease
#4
Elodie Persyn, Matilde Karakachoff, Solena Le Scouarnec, Camille Le Clézio, Dominique Campion, French Exome Consortium, Jean-Jacques Schott, Richard Redon, Lise Bellanger, Christian Dina
Next-generation sequencing technologies made it possible to assay the effect of rare variants on complex diseases. As an extension of the "common disease-common variant" paradigm, rare variant studies are necessary to get a more complete insight into the genetic architecture of human traits. Association studies of these rare variations show new challenges in terms of statistical analysis. Due to their low frequency, rare variants must be tested by groups. This approach is then hindered by the fact that an unknown proportion of the variants could be neutral...
2017: PloS One
https://www.readbyqxmd.com/read/28742084/systematic-tissue-specific-functional-annotation-of-the-human-genome-highlights-immune-related-dna-elements-for-late-onset-alzheimer-s-disease
#5
Qiongshi Lu, Ryan L Powles, Sarah Abdallah, Derek Ou, Qian Wang, Yiming Hu, Yisi Lu, Wei Liu, Boyang Li, Shubhabrata Mukherjee, Paul K Crane, Hongyu Zhao
Continuing efforts from large international consortia have made genome-wide epigenomic and transcriptomic annotation data publicly available for a variety of cell and tissue types. However, synthesis of these datasets into effective summary metrics to characterize the functional non-coding genome remains a challenge. Here, we present GenoSkyline-Plus, an extension of our previous work through integration of an expanded set of epigenomic and transcriptomic annotations to produce high-resolution, single tissue annotations...
July 24, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28741694/reduced-parahippocampal-volume-and-psychosis-symptoms-in-alzheimer-s-disease
#6
Emma McLachlan, Jennifer Bousfield, Robert Howard, Suzanne Reeves
OBJECTIVE: Establishing structural imaging correlates of psychosis symptoms in Alzheimer's disease (AD) could localise pathology and target symptomatic treatment. This study investigated whether psychosis symptoms are associated with visuoperceptual or frontal networks, and whether regional brain volume differences could be linked with the paranoid (persecutory delusions) or misidentification (misidentification phenomena and/or hallucinations) subtypes. METHODS: A total of 104 patients with probable AD (AddNeuroMed; 47 psychotic, 57 non-psychotic), followed up for at least one year with structural MRI at baseline...
July 25, 2017: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28741672/finding-of-increased-caudate-nucleus-in-patients-with-alzheimer-s-disease
#7
K Persson, V D Bohbot, N Bogdanovic, G Selbaek, A Braekhus, K Engedal
OBJECTIVES: A recently published study using an automated MRI volumetry method (NeuroQuant®) unexpectedly demonstrated larger caudate nucleus volume in patients with Alzheimer's disease dementia (AD) compared to patients with subjective and mild cognitive impairment (SCI and MCI). The aim of this study was to explore this finding. MATERIALS & METHODS: The caudate nucleus and the hippocampus volumes were measured (both expressed as ratios of intracranial volume) in a total of 257 patients with SCI and MCI according to the Winblad criteria and AD according to ICD-10 criteria...
July 25, 2017: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/28741645/inflammasome-and-autophagy-regulation-a-two-way-street
#8
Qian Sun, Jie Fan, Timothy R Billiar, Melanie J Scott
Inflammation plays a significant role in protecting hosts against pathogens. Inflammation induced by non-infectious, endogenous agents can be detrimental, and if excessive can result in organ and tissue damage. The inflammasome is a major innate immune pathway that can be activated via both exogenous pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs). Inflammasome activation involves formation and oligomerization of a protein complex including a NOD-like receptor (NLR), an adaptor protein (ASC) and procaspase-1...
July 24, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28741167/microvascular-ultrastructural-changes-precede-cognitive-impairment-in-the-murine-appswe-ps1de9-model-of-alzheimer-s-disease
#9
Patricia Kelly, Paul Denver, Simon C Satchell, Maximilian Ackermann, Moritz A Konerding, Christopher A Mitchell
Cerebral and systemic organ microvascular pathologies coexist with human Alzheimer's disease (AD) neuropathology. In this study, we hypothesised that both cerebral and systemic microvascular pathologies exist in 4- to 5-month-old male APPswe/PS1dE9 (APP/PS1) transgenic mice prior to the onset of cognitive impairment. To assess this we examined recognition memory in both wild-type and APP/PS1 mice using the object recognition task (ORT; n = 11 per group) and counted thioflavin-S-positive plaques in brain (n = 6 per group)...
July 25, 2017: Angiogenesis
https://www.readbyqxmd.com/read/28741112/investigation-of-naphthofuran-moiety-as-potential-dual-inhibitor-against-bace-1-and-gsk-3%C3%AE-molecular-dynamics-simulations-binding-energy-and-network-analysis-to-identify-first-in-class-dual-inhibitors-against-alzheimer-s-disease
#10
Akhil Kumar, Gaurava Srivastava, Swati Srivastava, Seema Verma, Arvind S Negi, Ashok Sharma
BACE-1 and GSK-3β are potential therapeutic drug targets for Alzheimer's disease. Recently, both the targets received attention for designing dual inhibitors for Alzheimer's disease. Until now, only two-scaffold triazinone and curcumin have been reported as BACE-1 and GSK-3β dual inhibitors. Docking, molecular dynamics, clustering, binding energy, and network analysis of triazinone derivatives with BACE-1 and GSK-3β was performed to get molecular insight into the first reported dual inhibitor. Further, we designed and evaluated a naphthofuran series for its ability to inhibit BACE-1 and GSK-3β with the computational approaches...
August 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28740740/environmental-factors-promoting-neural-plasticity-insights-from-animal-and-human-studies
#11
REVIEW
Laura Mandolesi, Francesca Gelfo, Laura Serra, Simone Montuori, Arianna Polverino, Giuseppe Curcio, Giuseppe Sorrentino
We do not all grow older in the same way. Some individuals have a cognitive decline earlier and faster than others who are older in years but cerebrally younger. This is particularly easy to verify in people who have maintained regular physical activity and healthy and cognitively stimulating lifestyle and even in the clinical field. There are patients with advanced neurodegeneration, such as Alzheimer's disease (AD), that, despite this, have mild cognitive impairment. What determines this interindividual difference? Certainly, it cannot be the result of only genetic factors...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28740603/an-atr-ftir-sensor-unraveling-the-drug-intervention-of-methylene-blue-congo-red-and-berberine-on-human-tau-and-a%C3%AE
#12
Jonas Schartner, Andreas Nabers, Brian Budde, Julia Lange, Nina Hoeck, Jens Wiltfang, Carsten Kötting, Klaus Gerwert
Alzheimer's disease affects millions of human beings worldwide. The disease progression is characterized by the formation of plaques and neurofibrillary tangles in the brain, which are based on aggregation processes of the Aβ peptide and tau protein. Today there is no cure and even no in vitro assay available for the identification of drug candidates, which provides direct information concerning the protein secondary structure label-free. Therefore, we developed an attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) sensor, which uses surface bound antibodies to immobilize a desired target protein...
July 13, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28740390/brain-regions-associated-with-anosognosia-for-memory-disturbance-in-alzheimer-s-disease-a-magnetic-resonance-imaging-study
#13
Hiroshi Fujimoto, Teruyuki Matsuoka, Yuka Kato, Keisuke Shibata, Kaeko Nakamura, Kei Yamada, Jin Narumoto
BACKGROUND AND OBJECTIVE: Patients with Alzheimer's disease (AD) are frequently unaware of their cognitive symptoms and medical diagnosis. The term "anosognosia" is used to indicate a general lack of awareness of one's disease or disorder. The neural substrate underlying anosognosia in AD is unclear. Since anosognosia for memory disturbance might be an initial sign of AD, it is important to determine the neural correlates. This study was designed to investigate the characteristics and neural correlates of anosognosia for memory disturbance in patients with mild AD...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28739492/efficacy-and-safety-of-citalopram-compared-to-atypical-antipsychotics-on-agitation-in-nursing-home-residents-with-alzheimer-dementia
#14
Giovanni Viscogliosi, Iulia Maria Chiriac, Evaristo Ettorre
OBJECTIVE: To assess efficacy and safety of citalopram compared to quetiapine and olanzapine for the treatment of agitation in patients with Alzheimer disease (AD). DESIGN: Longitudinal, 6-month study. SETTING: Nursing home (NH). PARTICIPANTS: 75 NH residents with AD and agitation, randomized to citalopram (n = 25), quetiapine (n = 25), or olanzapine (n = 25). MEASUREMENTS: Changes in Neuropsychiatric Inventory (NPI) agitation subscale score and the modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC) were used to assess treatment efficacy...
July 21, 2017: Journal of the American Medical Directors Association
https://www.readbyqxmd.com/read/28739324/reaction-based-small-molecule-fluorescent-probes-for-dynamic-detection-of-ros-and-transient-redox-changes-in-living-cells-and-small-animals
#15
REVIEW
Rui Lü
Dynamic detection of transient redox changes in living cells and animals has broad implications for human health and disease diagnosis, because intracellular redox homeostasis regulated by reactive oxygen species (ROS) plays important role in cell functions, normal physiological functions and some serious human diseases (e.g., cancer, Alzheimer's disease, diabetes, etc.) usually have close relationship with the intracellular redox status. Small-molecule ROS-responsive fluorescent probes can act as powerful tools for dynamic detection of ROS and redox changes in living cells and animals through fluorescence imaging techniques; and great advances have been achieved recently in the design and synthesis of small-molecule ROS-responsive fluorescent probes...
July 21, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28739183/can-crosstalk-between-dor-and-parp-reduce-oxidative-stress-mediated-neurodegeneration
#16
REVIEW
Rutika Raina, Dwaipayan Sen
The progressive loss of structure and function of neurons leads to neurodegenerative processes which become the causative reason for various neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD) etc. These diseases are multifactorial in nature but they have been seen to possess similar causative agents to a certain extent. Oxidative Stress (OS) has been identified as a major stressor and a mediator in most of these diseases. OS not only leads to the generation of free radical species but if persistent, can possibly lead to lipid peroxidation, protein damage, DNA damage, and cell death...
July 21, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28738770/effects-of-resveratrol-and-other-polyphenols-on-the-most-common-brain-age-related-diseases
#17
Fiorella Sarubbo, David Moranta, Victor Jose Asensio, Antonio Miralles, Susana Esteban
With the global increase in the elderly population, modern societies must meet the challenge to find strategies to reduce the consequences of aging process; thereby decreasing the incidence of age-related neurodegenerative diseases. Over the last two decades, oxidative stress and recently inflammation, have been pointed out as the leading causes of brain aging. As a suggested treatment, the consumption or administration of antioxidant and anti-inflammatory molecules, such as polyphenols, present in food, is recommended as a beneficial strategy for preventing brain aging and several brain age-related diseases...
July 24, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28738188/sleep-characteristics-and-risk-of-dementia-and-alzheimer-s-disease-the-atherosclerosis-risk-in-communities-study
#18
Pamela L Lutsey, Jeffrey R Misialek, Thomas H Mosley, Rebecca F Gottesman, Naresh M Punjabi, Eyal Shahar, Richard MacLehose, Rachel P Ogilvie, David Knopman, Alvaro Alonso
INTRODUCTION: This study tested the hypotheses that late-midlife obstructive sleep apnea (OSA) and short and long sleep duration are associated with dementia for more than 15 years of follow-up. METHODS: A total of 1667 Atherosclerosis Risk in Communities Study participants underwent in-home polysomnography (1996-1998) and were followed for dementia. Dementia was defined by (1) hospitalization diagnosis codes (1996-2012) and (2) a comprehensive neurocognitive examination (2011-2013) with adjudication...
July 21, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28738187/presymptomatic-atrophy-in-autosomal-dominant-alzheimer-s-disease-a%C3%A2-serial-mri-study
#19
Kirsi M Kinnunen, David M Cash, Teresa Poole, Chris Frost, Tammie L S Benzinger, R Laila Ahsan, Kelvin K Leung, M Jorge Cardoso, Marc Modat, Ian B Malone, John C Morris, Randall J Bateman, Daniel S Marcus, Alison Goate, Stephen Salloway, Stephen Correia, Reisa A Sperling, Jasmeer P Chhatwal, Richard Mayeux, Adam M Brickman, Ralph N Martins, Martin R Farlow, Bernardino Ghetti, Andrew J Saykin, Clifford R Jack, Peter R Schofield, Eric McDade, Michael W Weiner, John M Ringman, Paul M Thompson, Colin L Masters, Christopher C Rowe, Martin N Rossor, Sebastien Ourselin, Nick C Fox
INTRODUCTION: Identifying at what point atrophy rates first change in Alzheimer's disease is important for informing design of presymptomatic trials. METHODS: Serial T1-weighed magnetic resonance imaging scans of 94 participants (28 noncarriers, 66 carriers) from the Dominantly Inherited Alzheimer Network were used to measure brain, ventricular, and hippocampal atrophy rates. For each structure, nonlinear mixed-effects models estimated the change-points when atrophy rates deviate from normal and the rates of change before and after this point...
July 21, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28738127/early-onset-alzheimer-disease-and-candidate-risk-genes-involved-in-endolysosomal-transport
#20
Brian W Kunkle, Badri N Vardarajan, Adam C Naj, Patrice L Whitehead, Sophie Rolati, Susan Slifer, Regina M Carney, Michael L Cuccaro, Jeffery M Vance, John R Gilbert, Li-San Wang, Lindsay A Farrer, Christiane Reitz, Jonathan L Haines, Gary W Beecham, Eden R Martin, Gerard D Schellenberg, Richard P Mayeux, Margaret A Pericak-Vance
Importance: Mutations in APP, PSEN1, and PSEN2 lead to early-onset Alzheimer disease (EOAD) but account for only approximately 11% of EOAD overall, leaving most of the genetic risk for the most severe form of Alzheimer disease unexplained. This extreme phenotype likely harbors highly penetrant risk variants, making it primed for discovery of novel risk genes and pathways for AD. Objective: To search for rare variants contributing to the risk for EOAD. Design, Setting, and Participants: In this case-control study, whole-exome sequencing (WES) was performed in 51 non-Hispanic white (NHW) patients with EOAD (age at onset <65 years) and 19 Caribbean Hispanic families previously screened as negative for established APP, PSEN1, and PSEN2 causal variants...
July 24, 2017: JAMA Neurology
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