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https://www.readbyqxmd.com/read/29145658/characterization-of-detergent-insoluble-proteome-in-chronic-traumatic-encephalopathy
#1
Jonathan D Cherry, Ahmad Zeineddin, Eric B Dammer, James A Webster, Duc Duong, Nicholas T Seyfried, Allan I Levey, Victor E Alvarez, Bertrand R Huber, Thor D Stein, Patrick T Kiernan, Ann C McKee, James J Lah, Chadwick M Hales
Quantitative proteomics of postmortem human brain can identify dysfunctional proteins that contribute to neurodegenerative disorders like Alzheimer disease (AD) and frontotemporal dementia. Similar studies in chronic traumatic encephalopathy (CTE) are limited, therefore we hypothesized that proteomic sequencing of CTE frontal cortex brain homogenates from varying CTE pathologic stages may provide important new insights into this disorder. Quantitative proteomics of control, CTE and AD brains was performed to characterize differentially expressed proteins, and we identified over 4000 proteins in CTE brains, including significant enrichment of the microtubule associated protein tau...
November 14, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29144001/biological-evaluation-and-energetic-analyses-of-novel-gsk-3%C3%AE-inhibitors
#2
Denan Zhang, Lei Liu, Lin Pang, Qing Jin, Kehui Ke, Ming Hu, Jingbo Yang, Weifang Ma, Hongbo Xie, Xiujie Chen
Glycogen synthase kinase-3 beta (GSK-3β) is involved in multiple signaling pathways. Consistent with its critical roles in normal cells, abnormalities in GSK-3β activity have been implicated in diabetes, heart disease, Parkinson disease and Alzheimer's disease. In this study, a series of new scaffolds of small molecule inhibitors of GSK-3β were identified by virtual screening and bioassay. Candidates that adhere to drug-like criteria from a virtual library of compounds were tested using computational docking studies...
November 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29143870/head-to-head-comparison-of-18-f-av-1451-and-18-f-thk5351-for-tau-imaging-in-alzheimer-s-disease-and-frontotemporal-dementia
#3
Young Kyoung Jang, Chul Hyoung Lyoo, Seongbeom Park, Seung Jun Oh, Hanna Cho, Minyoung Oh, Young Hoon Ryu, Jae Yong Choi, Gil D Rabinovici, Hee Jin Kim, Seung Hwan Moon, Hyemin Jang, Jin San Lee, William J Jagust, Duk L Na, Jae Seung Kim, Sang Won Seo
PURPOSE: Tau accumulation is a core pathologic change in various neurodegenerative diseases including Alzheimer's disease and frontotemporal lobar degeneration-tau. Recently, tau positron emission tomography tracers such as [(18)F] AV-1451 and [(18)F] THK5351 have been developed to detect tau deposition in vivo. In the present study, we performed a head to head comparison of these two tracers in Alzheimer's disease and frontotemporal dementia cases and aimed to investigate which tracers are better suited to image tau in these disorders...
November 16, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29143759/the-role-of-food-antioxidants-benefits-of-functional-foods-and-influence-of-feeding-habits-on-the-health-of-the-older-person-an-overview
#4
REVIEW
Douglas W Wilson, Paul Nash, Harpal Singh Buttar, Keith Griffiths, Ram Singh, Fabien De Meester, Rie Horiuchi, Toru Takahashi
This overview was directed towards understanding the relationship of brain functions with dietary choices mainly by older humans. This included food color, flavor, and aroma, as they relate to dietary sufficiency or the association of antioxidants with neurodegenerative diseases such as dementia and Alzheimer's disease. Impairment of olfactory and gustatory function in relation to these diseases was also explored. The role of functional foods was considered as a potential treatment of dementia and Alzheimer's disease through inhibition of acetylcholinesterase as well as similar treatments based on herbs, spices and antioxidants therein...
October 28, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29143702/association-between-altered-neurochemical-metabolites-and-apathy-in-patients-with-alzheimer-s-disease
#5
Yi-Chun Yeh, Chun-Wei Li, Yu-Ting Kuo, Mei-Feng Huang, Tai-Ling Liu, Twei-Shiun Jaw, Yi-Hsin Yang, Kuang-Che Kuo, Cheng-Sheng Chen
BACKGROUND: Apathy is a condition characterized by a lack of motivation that manifests in emotional, behavioral, and cognitive domains. Although previous studies have indicated that apathy is associated with frontal lesions, few studies have focused on the different subdomains of apathy, and no in vivo human biochemical data have been obtained to examine the neurochemical changes related to apathy in patients with Alzheimer's disease (AD). Thus, we investigated the frontal neurochemical alterations related to apathy among patients with AD using proton magnetic resonance spectroscopy (1H MRS)...
November 16, 2017: International Psychogeriatrics
https://www.readbyqxmd.com/read/29143445/glycyrrhiza-uralensis-and-semilicoisoflavone-b-reduce-a%C3%AE-secretion-by-increasing-ppar%C3%AE-expression-and-inhibiting-stat3-phosphorylation-to-inhibit-bace1-expression
#6
Ming-Yao Gu, Yoon Sun Chun, Dong Zhao, Ryu Shi Yong, Hyun Ok Yang
SCOPE: Glycyrrhiza uralensis extract (GUE) has been reported to improve amyloid beta (Aβ) induced cognitive deficits in mice. However, the mechanisms underlying this effect and the components involved have not been previously explored. Extracellular Aβ plaques are one of the major pathological hallmarks of Alzheimer's disease (AD). Therefore, decreasing Aβ levels is one strategy for preventing the etiology of AD. This study aimed to test the effect of GUE and semilicoisoflavone B (SB) on Aβ secretion and investigate the mechanism underlying this effect...
November 16, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29143372/a-critical-role-of-trpm2-channel-in-a%C3%AE-42-induced-microglial-activation-and-generation-of-tumor-necrosis-factor-%C3%AE
#7
Sharifah Alawieyah Syed Mortadza, Joan A Sim, Veronika E Neubrand, Lin-Hua Jiang
Amyloid β (Aβ)-induced neuroinflammation plays an important part in Alzheimer's disease (AD). Emerging evidence supports a role for the transient receptor potential melastatin-related 2 (TRPM2) channel in Aβ-induced neuroinflammation, but how Aβ induces TRPM2 channel activation and this relates to neuroinflammation remained poorly understood. We investigated the mechanisms by which Aβ42 activates the TRPM2 channel in microglial cells and the relationships to microglial activation and generation of tumor necrosis factor-α (TNF-α), a key cytokine implicated in AD...
November 16, 2017: Glia
https://www.readbyqxmd.com/read/29143367/risk-of-death-associated-with-new-benzodiazepine-use-among-persons-with-alzheimer-disease-a-matched-cohort-study
#8
Laura Saarelainen, Anna-Maija Tolppanen, Marjaana Koponen, Antti Tanskanen, Jari Tiihonen, Sirpa Hartikainen, Heidi Taipale
OBJECTIVE: To investigate the risk of death associated with new benzodiazepine and related drug (BZDR) use in a nationwide cohort of persons with Alzheimer disease (AD). METHODS: The register-based MEDALZ cohort, including all community-dwelling Finns diagnosed with AD during 2005 to 2011 (n = 70 718), was used. Clinically verified AD diagnoses were obtained from the Special Reimbursement Register. Drug use periods were modeled from BZDR purchases, derived from the Prescription Register...
November 15, 2017: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/29143217/fluid-biomarker-agreement-and-interrelation-in-dementia-due-to-alzheimer-s-disease
#9
Panagiotis Alexopoulos, Jennifer Roesler, Lukas Werle, Nathalie Thierjung, Iliana Lentzari, Marion Ortner, Timo Grimmer, Nikolaos Laskaris, Antonios Politis, Philippos Gourzis, Alexander Kurz, Robert Perneczky
The cerebrospinal fluid (CSF) levels of β-amyloid 42, total tau, and phosphorylated tau 181 are supposed to be all continuously abnormal in dementia due to Alzheimer's disease (AD), being the most advanced disease stage. The aim of the present study, which included a monocentric and a multicentric sample (N = 119 and 178, respectively), was to investigate the degree of CSF biomarker agreement and interrelation in AD dementia. Based on previously published cut-off values, biomarker values were categorized as positive or negative for AD (dichotomization strategy) and as either positive, negative, or borderline (trichotomization strategy)...
November 15, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29142396/antioxidant-and-cholinesterase-inhibitory-activities-of-ethyl-acetate-extract-of-terminalia-chebula-cell-free-in-vitro-and-in-silico-studies
#10
Mohamed Asik Rajmohamed, Suganthy Natarajan, Premkumar Palanisamy, Akbarsha Mohammad Abdulkader, Archunan Govindaraju
Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder clinically characterized by memory loss and impaired cognitive function. Cholinergic enzyme deficiency and oxidative stress are the two major factors implicated in the pathogenesis of AD. The symptomatic treatment, as of now, is the use of cholinesterase inhibitors toward cholinergic "downturn." Therefore, there is a search for compounds that will be useful in focused therapies. There has been suggestion that Terminalia chebula fruit would be a potential source...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29142315/hiv-1-counteracts-an-innate-restriction-by-amyloid-precursor-protein-resulting-in-neurodegeneration
#11
Qingqing Chai, Vladimir Jovasevic, Viacheslav Malikov, Yosef Sabo, Scott Morham, Derek Walsh, Mojgan H Naghavi
While beta-amyloid (Aβ), a classic hallmark of Alzheimer's disease (AD) and dementia, has long been known to be elevated in the human immunodeficiency virus type 1 (HIV-1)-infected brain, why and how Aβ is produced, along with its contribution to HIV-associated neurocognitive disorder (HAND) remains ill-defined. Here, we reveal that the membrane-associated amyloid precursor protein (APP) is highly expressed in macrophages and microglia, and acts as an innate restriction against HIV-1. APP binds the HIV-1 Gag polyprotein, retains it in lipid rafts and blocks HIV-1 virion production and spread...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29142266/hyperspectral-raman-imaging-of-neuritic-plaques-and-neurofibrillary-tangles-in-brain-tissue-from-alzheimer-s-disease-patients
#12
Ralph Michael, Aufried Lenferink, Gijs F J M Vrensen, Ellen Gelpi, Rafael I Barraquer, Cees Otto
Neuritic plaques and neurofibrillary tangles are crucial morphological criteria for the definite diagnosis of Alzheimer's disease. We evaluated 12 unstained frontal cortex and hippocampus samples from 3 brain donors with Alzheimer's disease and 1 control with hyperspectral Raman microscopy on samples of 30 × 30 µm. Data matrices of 64 × 64 pixels were used to quantify different tissue components including proteins, lipids, water and beta-sheets for imaging at 0.47 µm spatial resolution. Hierarchical cluster analysis was performed to visualize regions with high Raman spectral similarities...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29142239/differential-overexpression-of-serpina3-in-human-prion-diseases
#13
S Vanni, F Moda, M Zattoni, E Bistaffa, E De Cecco, M Rossi, G Giaccone, F Tagliavini, S Haïk, J P Deslys, G Zanusso, J W Ironside, I Ferrer, G G Kovacs, G Legname
Prion diseases are fatal neurodegenerative disorders with sporadic, genetic or acquired etiologies. The molecular alterations leading to the onset and the spreading of these diseases are still unknown. In a previous work we identified a five-gene signature able to distinguish intracranially BSE-infected macaques from healthy ones, with SERPINA3 showing the most prominent dysregulation. We analyzed 128 suitable frontal cortex samples, from prion-affected patients (variant Creutzfeldt-Jakob disease (vCJD) n = 20, iatrogenic CJD (iCJD) n = 11, sporadic CJD (sCJD) n = 23, familial CJD (gCJD) n = 17, fatal familial insomnia (FFI) n = 9, Gerstmann-Sträussler-Scheinker syndrome (GSS)) n = 4), patients with Alzheimer disease (AD, n = 14) and age-matched controls (n = 30)...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29142143/dha-supplementation-improves-cognitive-function-via-enhancing-a%C3%AE-mediated-autophagy-in-chinese-elderly-with-mild-cognitive-impairment-a-randomised-placebo-controlled-trial
#14
Yan-Ping Zhang, Yinyin Lou, Jing Hu, Rujuan Miao, Fei Ma
BACKGROUND: Higher docosahexaenoic acid (DHA) intake is inversely correlated with relative risk of Alzheimer's disease. The potential benefits of DHA supplementation in people with mild cognitive impairment (MCI) have not been fully examined. OBJECTIVE: Our study aimed to assess the effect of a 24-month DHA supplementation on cognitive function and amyloid beta (Aβ)-mediated autophagy in elderly subjects with MCI. METHODS: This was a randomised, double-blind, placebo-controlled trial in Tianjin, China...
November 15, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29142140/imaging-and-csf-analyses-effectively-distinguish-cjd-from-its-mimics
#15
Peter Rudge, Harpreet Hyare, Alison Green, John Collinge, Simon Mead
OBJECTIVE: To review clinical and investigation findings in patients referred to a specialist prion clinic who were suspected to have sporadic Creutzfeldt-Jakob disease (sCJD) and yet were found to have an alternative final diagnosis. METHODS: Review the clinical findings and investigations in 214 patients enrolled into the UK National Prion Monitoring Cohort Study between October 2008 and November 2015 who had postmortem confirmed sCJD and compare these features with 50 patients referred over the same period who had an alternative final diagnosis (CJD mimics)...
November 15, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29142138/chitotriosidase-chit1-is-increased-in-microglia-and-macrophages-in-spinal-cord-of-amyotrophic-lateral-sclerosis-and-cerebrospinal-fluid-levels-correlate-with-disease-severity-and-progression
#16
Petra Steinacker, Federico Verde, Lubin Fang, Emily Feneberg, Patrick Oeckl, Sigrun Roeber, Sarah Anderl-Straub, Adrian Danek, Janine Diehl-Schmid, Klaus Fassbender, Klaus Fliessbach, Hans Foerstl, Armin Giese, Holger Jahn, Jan Kassubek, Johannes Kornhuber, G Bernhard Landwehrmeyer, Martin Lauer, Elmar Hans Pinkhardt, Johannes Prudlo, Angela Rosenbohm, Anja Schneider, Matthias L Schroeter, Hayrettin Tumani, Christine A F von Arnim, Jochen Weishaupt, Patrick Weydt, Albert C Ludolph, Deniz Yilmazer Hanke, Markus Otto
OBJECTIVES: Neurochemical markers of amyotrophic lateral sclerosis (ALS) that reflect underlying disease mechanisms might help in diagnosis, staging and prediction of outcome. We aimed at determining the origin and differential diagnostic and prognostic potential of the putative marker of microglial activation chitotriosidase (CHIT1). METHODS: Altogether 316 patients were included, comprising patients with sporadic ALS, ALS mimics (disease controls (DCo)), frontotemporal lobar degeneration (FTLD), Creutzfeldt-Jakob disease (CJD), Alzheimer's disease (AD), Parkinson's disease (PD) and healthy controls (Con)...
November 15, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29142106/soluble-a%C3%AE-aggregates-can-inhibit-prion-propagation
#17
Claire J Sarell, Emma Quarterman, Daniel C-M Yip, Cassandra Terry, Andrew J Nicoll, Jonathan D F Wadsworth, Mark A Farrow, Dominic M Walsh, John Collinge
Mammalian prions cause lethal neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD) and consist of multi-chain assemblies of misfolded cellular prion protein (PrP(C)). Ligands that bind to PrP(C) can inhibit prion propagation and neurotoxicity. Extensive prior work established that certain soluble assemblies of the Alzheimer's disease (AD)-associated amyloid β-protein (Aβ) can tightly bind to PrP(C), and that this interaction may be relevant to their toxicity in AD. Here, we investigated whether such soluble Aβ assemblies might, conversely, have an inhibitory effect on prion propagation...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29141990/rna-sequencing-of-drosophila-melanogaster-head-tissue-on-high-sugar-and-high-fat-diets
#18
Wayne Hemphill, Osvaldo Rivera, Matthew Talbert
Obesity has been shown to increase risk for cardiovascular disease and type-2 diabetes. In addition, it has been implicated in aggravation of neurological conditions such as Alzheimer's. In the model organism Drosophila melanogaster, a physiological state mimicking diet-induced obesity can be induced by subjecting fruit flies to a solid medium disproportionately higher in sugar than protein or that has been supplemented with a rich source of saturated fat. These flies can exhibit increased circulating glucose levels, increased triglyceride content, insulin-like peptide resistance, and behavior indicative of neurological decline...
November 15, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29141977/vitamins-associated-with-brain-aging-mild-cognitive-impairment-and-alzheimer-disease-biomarkers-epidemiological-and-experimental-evidence-plausible-mechanisms-and-knowledge-gaps
#19
REVIEW
Michael Fenech
The key to preventing brain aging, mild cognitive impairment (MCI), and Alzheimer disease (AD) via vitamin intake is first to understand molecular mechanisms, then to deduce relevant biomarkers, and subsequently to test the level of evidence for the impact of vitamins in the relevant pathways and their modulation of dementia risk. This narrative review infers information on mechanisms from gene and metabolic defects associated with MCI and AD, and assesses the role of vitamins using recent results from animal and human studies...
November 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/29141953/amyloid-%C3%AE-42-peptide-is-toxic-to-non-neural-cells-in-drosophila-yielding-a-characteristic-metabolite-profile-and-the-effect-can-be-suppressed-by-pi3k
#20
Mercedes Arnés, Sergio Casas-Tintó, Anders Malmendal, Alberto Ferrús
The human Aβ42 peptide is associated with Alzheimer's disease through its deleterious effects in neurons. Expressing the human peptide in adult Drosophila in a tissue- and time-controlled manner, we show that Aβ42 is also toxic in non-neural cells, neurosecretory and epithelial cell types in particular. This form of toxicity includes the aberrant signaling by Wingless morphogen leading to the eventual activation of Caspase 3. Preventing Caspase 3 activation by means of p53 keeps epithelial cells from elimination but maintains the Aβ42 toxicity yielding more severe deleterious effects to the organism...
November 15, 2017: Biology Open
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