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https://www.readbyqxmd.com/read/28087578/distinct-binding-of-pet-ligands-pbb3-and-av-1451-to-tau-fibril-strains-in-neurodegenerative-tauopathies
#1
Maiko Ono, Naruhiko Sahara, Katsushi Kumata, Bin Ji, Ruiqing Ni, Shunsuke Koga, Dennis W Dickson, John Q Trojanowski, Virginia M-Y Lee, Mari Yoshida, Isao Hozumi, Yasumasa Yoshiyama, John C van Swieten, Agneta Nordberg, Tetsuya Suhara, Ming-Rong Zhang, Makoto Higuchi
Diverse neurodegenerative disorders are characterized by deposition of tau fibrils composed of conformers (i.e. strains) unique to each illness. The development of tau imaging agents has enabled visualization of tau lesions in tauopathy patients, but the modes of their binding to different tau strains remain elusive. Here we compared binding of tau positron emission tomography ligands, PBB3 and AV-1451, by fluorescence, autoradiography and homogenate binding assays with homologous and heterologous blockades using tauopathy brain samples...
January 12, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28086931/the-release-and-trans-synaptic-transmission-of-tau-via-exosomes
#2
Yipeng Wang, Varun Balaji, Senthilvelrajan Kaniyappan, Lars Krüger, Stephan Irsen, Katharina Tepper, RamReddy Chandupatla, Walter Maetzler, Anja Schneider, Eckhard Mandelkow, Eva-Maria Mandelkow
BACKGROUND: Tau pathology in AD spreads in a hierarchical pattern, whereby it first appears in the entorhinal cortex, then spreads to the hippocampus and later to the surrounding areas. Based on this sequential appearance, AD can be classified into six stages ("Braak stages"). The mechanisms and agents underlying the progression of Tau pathology are a matter of debate. Emerging evidence indicates that the propagation of Tau pathology may be due to the transmission of Tau protein, but the underlying pathways and Tau species are not well understood...
January 13, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28086917/resveratrol-regulates-neuro-inflammation-and-induces-adaptive-immunity-in-alzheimer-s-disease
#3
Charbel Moussa, Michaeline Hebron, Xu Huang, Jaeil Ahn, Robert A Rissman, Paul S Aisen, R Scott Turner
BACKGROUND: Treatment of mild-moderate Alzheimer's disease (AD) subjects (N = 119) for 52 weeks with the SIRT1 activator resveratrol (up to 1 g by mouth twice daily) attenuates progressive declines in CSF Aβ40 levels and activities of daily living (ADL) scores. METHODS: For this retrospective study, we examined banked CSF and plasma samples from a subset of AD subjects with CSF Aβ42 <600 ng/ml (biomarker-confirmed AD) at baseline (N = 19 resveratrol-treated and N = 19 placebo-treated)...
January 3, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28079886/hiv-1-nef-is-released-in-extracellular-vesicles-derived-from-astrocytes-evidence-for-nef-mediated-neurotoxicity
#4
A Sami Saribas, Stephanie Cicalese, Taha Mohseni Ahooyi, Kamel Khalili, Shohreh Amini, Ilker Kudret Sariyer
Human immunodeficiency virus-associated neurological disorders (HANDs) affect the majority of AIDS patients and are a significant problem among HIV-1-infected individuals who live longer because of combined anti-retroviral therapies. HIV-1 utilizes a number of viral proteins and subsequent cytokine inductions to unleash its toxicity on neurons. Among HIV-1 viral proteins, Nef is a small protein expressed abundantly in astrocytes of HIV-1-infected brains and has been suggested to have a role in the pathogenesis of HAND...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28079535/heterozygous-deletion-of-chorein-exons-70-73-and-gna14-exons-3-7-in-a-brazilian-patient-presenting-with-probable-tau-negative-early-onset-alzheimer-disease
#5
Maciej J Lazarczyk, Sven Haller, Armand Savioz, Stefania Gimelli, Frédérique Bena, Panteleimon Giannakopoulos
No abstract text is available yet for this article.
January 10, 2017: Alzheimer Disease and Associated Disorders
https://www.readbyqxmd.com/read/28077397/relationships-between-flortaucipir-pet-tau-binding-and-amyloid-burden-clinical-diagnosis-age-and-cognition
#6
Michael J Pontecorvo, Michael D Devous, Michael Navitsky, Ming Lu, Stephen Salloway, Frederick W Schaerf, Danna Jennings, Anupa K Arora, Anne McGeehan, Nathaniel C Lim, Hui Xiong, Abhinay D Joshi, Andrew Siderowf, Mark A Mintun
The advent of tau-targeted positron emission tomography tracers such as flortaucipir ((18)F-AV-1451, also known as (18)F-T807) have made it possible to investigate the sequence of development of tau and amyloid-β in relationship to age, and to the development of cognitive impairment due to Alzheimer's disease. In this study, flortaucipir tau and florbetapir amyloid positron emission tomography were obtained for 217 subjects including 16 young and 58 older cognitively normal subjects, 95 subjects with mild cognitive impairment (Mini-Mental State Examination 24-30) and 48 subjects with clinically-defined possible or probable Alzheimer's disease (Mini-Mental State Examination >10)...
January 11, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28077166/threonine-175-a-novel-pathological-phosphorylation-site-on-tau-protein-linked-to-multiple-tauopathies
#7
Alexander J Moszczynski, Wencheng Yang, Robert Hammond, Lee Cyn Ang, Michael J Strong
Microtubule associated protein tau (tau) deposition is associated with a spectrum of neurodegenerative diseases collectively termed tauopathies. We have previously shown that amyotrophic lateral sclerosis (ALS) with cognitive impairment (ALSci) is associated with tau phosphorylation at Thr(175) and that this leads to activation of GSK3β which then induces phosphorylation at tau Thr(231). This latter step leads to dissociation of tau from microtubules and pathological tau fibril formation. To determine the extent to which this pathway is unique to ALS, we have investigated the expression of pThr(175) tau and pThr(231) tau across a range of frontotemporal degenerations...
January 11, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28077004/endoplasmic-reticulum-stress-modulation-as-a-target-for-ameliorating-effects-of-blast-induced-traumatic-brain-injury
#8
Brandon Peter Lucke-Wold, Aric Logsdon, Ryan C Turner, Jason D Huber, Charles L Rosen
Blast traumatic brain injury (bTBI) has been shown to contribute to progressive neurodegenerative disease. Recent evidence suggests that endoplasmic reticulum (ER) stress is a mechanistic link between acute neurotrauma and progressive tauopathy. We propose that ER stress contributes to extensive behavioral changes associated with a CTE-like phenotype. Targeting ER stress is a promising option for the treatment of neurotrauma related neurodegeneration warranting investigation. Utilizing our validated and clinically relevant Sprague-Dawley blast model, we investigated a time course of mechanistic changes that occur following bTBI (50 PSI) including: ER stress activation, iron mediated toxicity, and tauopathy via western blot and immunohistochemistry...
January 11, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28076358/a-randomized-trial-examining-housing-first-in-congregate-and-scattered-site-formats
#9
Julian M Somers, Akm Moniruzzaman, Michelle Patterson, Lauren Currie, Stefanie N Rezansoff, Anita Palepu, Karen Fryer
OBJECTIVE: No previous experimental trials have investigated Housing First (HF) in both scattered site (SHF) and congregate (CHF) formats. We hypothesized that CHF and SHF would be associated with a greater percentage of time stably housed as well as superior health and psychosocial outcomes over 24 months compared to treatment as usual (TAU). METHODS: Inclusion criteria were homelessness, mental illness, and high need for support. Participants were randomised to SHF, CHF, or TAU...
2017: PloS One
https://www.readbyqxmd.com/read/28075555/familial-mutations-may-switch-conformational-preferences-in-%C3%AE-synuclein-fibrils
#10
Liang Xu, Buyong Ma, Ruth Nussinov, Damien Thompson
The pathogenesis of Parkinson's disease is closely associated with the aggregation of the α-synuclein protein. Several familial mutants have been identified and shown to affect the aggregation kinetics of α-synuclein through distinct molecular mechanisms. Quantitative evaluation of the relative stabilities of the wild type and mutant fibrils is crucial for understanding the aggregation process and identifying the key component steps. In this work, we examined two topologically different α-synuclein fibril structures that are either determined by solid-state NMR method or modelled based on solid-state NMR data, and characterized their conformational properties and thermodynamic stabilities using molecular dynamics simulations...
January 11, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28074940/alpha7-nicotinic-acetylcholine-receptor-is-required-for-amyloid-pathology-in-brain-endothelial-cells-induced-by-glycoprotein-120-methamphetamine-and-nicotine
#11
Liqun Liu, Jingyi Yu, Li Li, Bao Zhang, Lingjuan Liu, Chun-Hua Wu, Ambrose Jong, Ding-An Mao, Sheng-He Huang
One of the most challenging issues in HIV-associated neurocognitive disorders (HAND) caused by HIV-1 virotoxins and drug abuse is the lack of understanding the underlying mechanisms that are commonly associated with disorders of the blood-brain barrier (BBB), which mainly consists of brain microvascular endothelial cells (BMEC). Here, we hypothesized that Glycoprotein 120 (gp120), methamphetamine (METH) and nicotine (NT) can enhance amyloid-beta (Aβ) accumulation in BMEC through Alpha7 nicotinic acetylcholine receptor (α7 nAChR)...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28073379/tau-passive-immunization-inhibits-not-only-tau-but-also-a%C3%AE-pathology
#12
Chun-Ling Dai, Yunn Chyn Tung, Fei Liu, Cheng-Xin Gong, Khalid Iqbal
BACKGROUND: Accumulation of hyperphosphorylated tau protein is a histopathological hallmark of Alzheimer's disease (AD) and related tauopathies. Currently, there is no effective treatment available for these progressive neurodegenerative diseases. In recent years, tau immunotherapy has shown great potential in animal models. We report the effect of immunization with tau antibodies 43D against tau 6-18 and 77E9 against tau 184-195 on tau and amyloid-β (Aβ) pathologies and cognition in triple-transgenic (3×Tg)-AD mice at mild to moderate stages of the disease...
January 10, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28073262/fluorescence-self-quenching-from-reporter-dyes-informs-on-the-structural-properties-of-amyloid-clusters-formed-in-vitro-and-in-cells
#13
WeiYue Chen, Laurence J Young, Meng Lu, Alessio Zaccone, Florian Ströhl, Na Yu, Gabriele S Kaminski Schierle, Clemens F Kaminski
The characterization of the aggregation kinetics of protein amyloids and the structural properties of the ensuing aggregates are vital in the study of the pathogenesis of many neurodegenerative diseases and the discovery of therapeutic targets. In this article, we show that the fluorescence lifetime of synthetic dyes covalently attached to amyloid proteins informs on the structural properties of amyloid clusters formed both in vitro and in cells. We demonstrate that the mechanism behind such a "lifetime sensor" of protein aggregation is based on fluorescence self-quenching and that it offers a good dynamic range to report on various stages of aggregation without significantly perturbing the process under investigation...
January 11, 2017: Nano Letters
https://www.readbyqxmd.com/read/28072416/preclinical-amyloid-pathology-biomarker-positivity-effects-on-tau-pathology-and-neurodegeneration
#14
K Höglund, S Kern, A Zettergren, A Börjesson-Hansson, H Zetterberg, I Skoog, K Blennow
Brain autopsy and biomarker studies indicate that the pathology of Alzheimer's disease (AD) is initiated at least 10-20 years before clinical symptoms. This provides a window of opportunity to initiate preventive treatment. However, this emphasizes the necessity for biomarkers that identify individuals at risk for developing AD later in life. In this cross-sectional study, originating from three epidemiologic studies in Sweden (n=1428), the objective was to examine whether amyloid pathology, as determined by low cerebrospinal fluid (CSF) concentration of the 42 amino acid form of β-amyloid (Aβ42), is associated with biomarker evidence of other pathological changes in cognitively healthy elderly...
January 10, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28071698/increased-levels-of-csf-total-but-not-oligomeric-or-phosphorylated-forms-of-alpha-synuclein-in-patients-diagnosed-with-probable-alzheimer-s-disease
#15
Nour K Majbour, Davide Chiasserini, Nishant N Vaikath, Paolo Eusebi, Takahiko Tokuda, Wilma van de Berg, Lucilla Parnetti, Paolo Calabresi, Omar M A El-Agnaf
Several studies reported an association between CSF alpha-synuclein (α-syn) and tau in Alzheimer's disease (AD), and demonstrated the significance of α-syn in improving the diagnostic sensitivity/specificity of classical AD CSF biomarkers. In the current study, we measured CSF levels of different α-syn species in a cohort of AD patients (n = 225) who showed a CSF profile typical of AD at baseline as well as in cognitively intact controls (n = 68). CSF total α-syn (t-α-syn) significantly increased in the AD group (p < 0...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28070672/opposing-effects-of-progranulin-deficiency-on-amyloid-and-tau-pathologies-via-microglial-tyrobp-network
#16
Hideyuki Takahashi, Zoe A Klein, Sarah M Bhagat, Adam C Kaufman, Mikhail A Kostylev, Tsuneya Ikezu, Stephen M Strittmatter
Progranulin (PGRN) is implicated in Alzheimer's disease (AD) as well as frontotemporal lobar degeneration. Genetic studies demonstrate an association of the common GRN rs5848 variant that results in reduced PGRN levels with increased risk for AD. However, the mechanisms by which PGRN reduction from the GRN AD risk variant or mutation exacerbates AD pathophysiology remain ill defined. Here, we show that the GRN AD risk variant has no significant effects on florbetapir positron emission tomographic amyloid imaging and cerebrospinal fluid (CSF) Aβ levels, whereas it is associated with increased CSF tau levels in human subjects of the Alzheimer's disease neuroimaging initiative studies...
January 9, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28069930/a-quantitative-analysis-of-brain-soluble-tau-and-the-tau-secretion-factor
#17
Pengcheng Han, Geidy Serrano, Thomas G Beach, Richard J Caselli, Junxiang Yin, Ningning Zhuang, Jiong Shi
Neurofibrillary tangles (NFTs) represent products of insoluble tau protein in the brains of patients with Alzheimer disease (AD). The cerebrospinal fluid (CSF) tau level is a biomarker in AD diagnosis. The soluble portion of tau protein in brain parenchyma is presumably the source for CSF tau but this has not previously been quantified. We measured CSF tau and soluble brain tau at autopsy in temporal and frontal brain tissue samples from 7 cognitive normal, 12 mild cognitively impaired, and 19 AD subjects. Based on the measured brain soluble tau, we calculated the whole brain tau load and estimated tau secretion factor...
January 9, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28069563/brief-cognitive-behavioural-therapy-for-patients-in-the-community-with-schizophrenia-randomised-controlled-trial-in-beijing-china
#18
Zhi-Hua Guo, Zhan-Jiang Li, Yun Ma, Jing Sun, Jun-Hua Guo, Wen-Xiu Li, Zhi-Qiang Wang, Hui-Li Xu, Roger M K Ng, Douglas Turkington, David Kingdon
BACKGROUND: Brief cognitive-behavioural therapy (CBT) is an emerging treatment for schizophrenia in community settings; however, further trials are needed, especially in non-Western countries. AIMS: To test the effects of brief CBT for Chinese patients with schizophrenia in the community (trial registration: ChiCTR-TRC-13003709). METHOD: A total of 220 patients with schizophrenia from four districts of Beijing were randomly assigned to either brief CBT plus treatment as usual (TAU) or TAU alone...
January 9, 2017: British Journal of Psychiatry: the Journal of Mental Science
https://www.readbyqxmd.com/read/28068845/post-traumatic-growth-in-adult-survivors-of-brain-injury-a-qualitative-study-of-participants-completing-a-pilot-trial-of-brief-positive-psychotherapy
#19
Olga Karagiorgou, Jonathan J Evans, Breda Cullen
PURPOSE: Post-traumatic growth (PTG) can occur following acquired brain injury (ABI). It has been proposed that people experiencing psychological distress following ABI may benefit from a positive psychotherapy intervention (PPT) aimed at increasing well-being; PPT may also influence PTG. We aimed to investigate PTG experiences in participants of a positive psychotherapy pilot trial. METHODS: ABI survivors who had received PPT or treatment as usual (TAU) were interviewed individually after the end of the trial...
January 9, 2017: Disability and Rehabilitation
https://www.readbyqxmd.com/read/28067492/the-polyphenol-altenusin-inhibits-in-vitro-fibrillization-of-tau-and-reduces-induced-tau-pathology-in-primary-neurons
#20
Sook Wern Chua, Alberto Cornejo, Janet van Eersel, Claire H Stevens, Inmaculada Vaca, Mercedes Cueto, Michael Kassiou, Amadeus Gladbach, Alex Macmillan, Lev Lewis, Renee Megan Whan, Lars Matthias Ittner
In Alzheimer´s disease the microtubule-associated protein tau forms intracellular neurofibrillary tangles (NFTs). A critical step in the formation of NFTs is the conversion of soluble tau into insoluble filaments. Accordingly, a current therapeutic strategy in clinical trials is aimed at preventing tau aggregation. Here, we assessed altenusin, a bioactive polyphenolic compound, for its potential to inhibit tau aggregation. Altenusin inhibits aggregation of tau protein into paired helical filaments in vitro...
January 9, 2017: ACS Chemical Neuroscience
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