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https://www.readbyqxmd.com/read/28453489/changes-of-cerebrospinal-fluid-peptides-due-to-tauopathy
#1
Petra Majerova, Peter Barath, Alena Michalicova, Stanislav Katina, Michal Novak, Andrej Kovac
Alzheimer's disease (AD) and progressive supranuclear palsy are two common neurodegenerative tauopathies, and the most common cause of progressive brain dementia in elderly affecting more than 35 million people. The tauopathies are characterized by abnormal deposition of microtubule associated protein tau into intracellular neurofibrillary tangles composed mainly of the hyperphosphorylated form of the protein. The diagnosis of tauopathies is based on the presence of clinical features and pathological changes...
April 27, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28453487/neuropsychiatric-symptoms-and-alzheimer-s-disease-biomarkers-predict-driving-decline-brief-report
#2
Ganesh M Babulal, Sarah H Stout, Denise Head, David M Holtzman, Anne M Fagan, John C Morris, Catherine M Roe
We examined whether neuropsychiatric symptoms (NPS) interact with cerebrospinal fluid (CSF) biomarkers (amyloid-β42 [Aβ42], tau, phosphorylated tau181 [ptau181], tau/Aβ42, and ptau181/Aβ42) of Alzheimer's disease pathology to predict driving decline among cognitively-normal older adults (N = 116) aged ≥65. Cox proportional hazards models examined time to receiving a rating of marginal or fail on the driving test. Age, education, and gender were adjusted in the models. Participants with more abnormal CSF (Aβ42, tau/Aβ42, ptau181/Aβ42) and NPS were faster to receive a marginal/fail on the road test compared to those without NPS...
April 28, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28446518/glutaminyl-cyclase-inhibitor-pq912-improves-cognition-in-mouse-models-of-alzheimer-s-disease-studies-on-relation-to-effective-target-occupancy
#3
Torsten Hoffmann, Antje Meyer, Ulrich Heiser, Stephan Kurat, Livia Bohme, Martin Kleinschmidt, Karl-Ulrich Buhring, Birgit Hutter-Paier, Martina Farcher, Hans-Ulrich Demuth, Inge Lues, Stephan Schilling
Numerous studies suggest that the majority of Aβ peptides deposited in Alzheimer's Disease (AD) is truncated and post-translationally modified at the N-terminus. Among these modified species, pyroglutamyl-Aβ (pE-Aβ including N3pE-Aβ42) has been identified as particularly neurotoxic. The N-terminal modification renders the peptide hydrophobic, accelerates formation of oligomers and reduces degradation by peptidases leading ultimately to the accumulation of the peptide and progression of AD. It has been shown, that the formation of pyroglutamyl residues is catalysed by glutaminyl cyclase (QC)...
April 26, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28441967/comparison-of-csf-markers-and-semi-quantitative-amyloid-pet-in-alzheimer-s-disease-diagnosis-and-in-cognitive-impairment-prognosis-using-the-adni-2-database
#4
Fayçal Ben Bouallègue, Denis Mariano-Goulart, Pierre Payoux
BACKGROUND: The relative performance of semi-quantitative amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) markers in diagnosing Alzheimer's disease (AD) and predicting the cognitive evolution of patients with mild cognitive impairment (MCI) is still debated. METHODS: Subjects from the Alzheimer's Disease Neuroimaging Initiative 2 with complete baseline cognitive assessment (Mini Mental State Examination, Clinical Dementia Rating [CDR] and Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-cog] scores), CSF collection (amyloid-β1-42 [Aβ], tau and phosphorylated tau) and (18)F-florbetapir scans were included in our cross-sectional cohort...
April 26, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28441961/the-influence-of-insulin-resistance-on-cerebrospinal-fluid-and-plasma-biomarkers-of-alzheimer-s-pathology
#5
REVIEW
Sarah Westwood, Benjamine Liu, Alison L Baird, Sneha Anand, Alejo J Nevado-Holgado, Danielle Newby, Maria Pikkarainen, Merja Hallikainen, Johanna Kuusisto, Johannes R Streffer, Gerald Novak, Kaj Blennow, Ulf Andreasson, Henrik Zetterberg, Ulf Smith, Markku Laakso, Hilkka Soininen, Simon Lovestone
BACKGROUND: Insulin resistance (IR) has previously been associated with an increased risk of developing Alzheimer's disease (AD), although the relationship between IR and AD is not yet clear. Here, we examined the influence of IR on AD using plasma and cerebrospinal fluid (CSF) biomarkers related to IR and AD in cognitively healthy men. We also aimed to characterise the shared protein signatures between IR and AD. METHODS: Fifty-eight cognitively healthy men, 28 IR and 30 non-IR (age and APOE ε4 matched), were drawn from the Metabolic Syndrome in Men study in Kuopio, Finland...
April 26, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28440221/nptx2-and-cognitive-dysfunction-in-alzheimer-s-disease
#6
Mei-Fang Xiao, Desheng Xu, Michael T Craig, Kenneth A Pelkey, Chun-Che Chien, Yang Shi, Juhong Zhang, Susan Resnick, Olga Pletnikova, David Salmon, James Brewer, Steven Edland, Jerzy Wegiel, Benjamin Tycko, Alena Savonenko, Roger H Reeves, Juan C Troncoso, Chris J McBain, Douglas Galasko, Paul F Worley
Memory loss in Alzheimer's disease (AD) is attributed to pervasive weakening and loss of synapses. Here, we present findings supporting a special role for excitatory synapses connecting pyramidal neurons of the hippocampus and cortex with fast-spiking parvalbumin (PV) interneurons that control network excitability and rhythmicity. Excitatory synapses on PV interneurons are dependent on the AMPA receptor subunit GluA4, which is regulated by presynaptic expression of the synaptogenic immediate early gene NPTX2 by pyramidal neurons...
March 23, 2017: ELife
https://www.readbyqxmd.com/read/28436390/biomarkers-for-early-diagnosis-of%C3%A2-alzheimer-s-disease-in-the-oldest-old-yes-or-no
#7
Lucia Paolacci, David Giannandrea, Patrizia Mecocci, Lucilla Parnetti
In recent years, many efforts have been spent to identify sensitive biomarkers able to improve the accuracy of Alzheimer's disease (AD) diagnosis. Two different workgroups (NIA-AA and IWG) included cerebrospinal fluid (CSF) and neuroimaging findings in their sets of criteria in order to improve diagnostic accuracy as well as early diagnosis. The number of subjects with cognitive impairment increases with aging but the oldest old (≥85 years of age), the fastest growing age group, is still the most unknown from a biological point of view...
April 15, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28435853/preclinical-alzheimer-s-disease-and-longitudinal-driving-decline
#8
Catherine M Roe, Ganesh M Babulal, Denise M Head, Sarah H Stout, Elizabeth K Vernon, Nupur Ghoshal, Brad Garland, Peggy P Barco, Monique M Williams, Ann Johnson, Rebecca Fierberg, M Scot Fague, Chengjie Xiong, Elizabeth Mormino, Elizabeth A Grant, David M Holtzman, Tammie L S Benzinger, Anne M Fagan, Brian R Ott, David B Carr, John C Morris
INTRODUCTION: Links between preclinical AD and driving difficulty onset would support the use of driving performance as an outcome in primary and secondary prevention trials among older adults (OAs). We examined whether AD biomarkers predicted the onset of driving difficulties among OAs. METHODS: 104 OAs (65+ years) with normal cognition took part in biomarker measurements, a road test, clinical and psychometric batteries and self-reported their driving habits. RESULTS: Higher values of CSF tau/Aβ42 and ptau181/Aβ42 ratios, but not uptake on PIB amyloid imaging (p=...
January 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/28434245/simultaneous-quantitation-of-the-bace1-inhibitor-azd3293-and-its-metabolite-az13569724-in-human-matrices-by-lc-ms-ms
#9
Yan Li, Paul H Severin, Mark R Hoffmann, Dennis L Miller, Scott A Monk, Alan R Kugler
AIM: AZD3293 is a novel BACE1 inhibitor in Phase III development for Alzheimer's disease. Sensitive and robust bioanalytical methods were required to quantitate AZD3293 and its metabolite AZ13569724 in human biological matrices. METHODOLOGY/RESULTS: Human plasma was prepared by protein precipitation. Linearity for both analytes was in the range of 0.5-500 ng/ml with up to 100-fold dilution. Plasma ultrafiltrate samples were prepared using Centrifree(®) ultrafiltration device...
April 24, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28430012/zo-1-expression-is-suppressed-by-gm-csf-via-mir-96-erg-in-brain-microvascular-endothelial-cells
#10
Hu Zhang, Shuhong Zhang, Jilin Zhang, Dongxin Liu, Jiayi Wei, Wengang Fang, Weidong Zhao, Yuhua Chen, Deshu Shang
The level of granulocyte-macrophage colony-stimulating factor (GM-CSF) increases in some disorders such as vascular dementia, Alzheimer's disease, and multiple sclerosis. We previously reported that in Alzheimer's disease patients, a high level of GM-CSF in the brain parenchyma downregulated expression of ZO-1, a blood-brain barrier tight junction protein, and facilitated the infiltration of peripheral monocytes across the blood-brain barrier. However, the molecular mechanism underlying regulation of ZO-1 expression by GM-CSF is unclear...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28426958/elucidating-the-role-of-trem2-in-alzheimer-s-disease
#11
REVIEW
Jason D Ulrich, Tyler K Ulland, Marco Colonna, David M Holtzman
Alzheimer's disease (AD) is the sixth leading cause of death in the United States and the most common cause of dementia in the elderly. Genetic factors, such as rare variants in the microglial-expressed gene TREM2, strongly impact the lifetime risk of developing AD. Several recent studies have described dramatic TREM2-dependent phenotypes in mouse models of amyloidosis that point to an important role for TREM2 in regulating the response of the innate immune system to Aβ pathology. Furthermore, elevations in the CSF levels of soluble TREM2 fragments implicate changes in inflammatory pathways as occurring coincident with markers of neuronal damage and the onset of clinical dementia in AD...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28417423/evaluation-of-the-expression-of-amyloid-precursor-protein-and-the-ratio-of-secreted-amyloid-beta-42-to-amyloid-beta-40-in-sh-sy5y-cells-stably-transfected-with-wild-type-single-mutant-and-double-mutant-forms-of-the-app-gene-for-the-study-of-alzheimer-s-disease
#12
Aslina Pahrudin Arrozi, Siti Nur Syazwani Shukri, Wan Zurinah Wan Ngah, Yasmin Anum Mohd Yusof, Mohd Hanafi Ahmad Damanhuri, Suzana Makpol
Neuroblastoma cell lines such as SH-SY5Y are the most frequently utilized models in neurodegenerative research, and their use has advanced the understanding of the pathology of neurodegeneration over the past few decades. In Alzheimer's disease (AD), several pathogenic mutations have been described, all of which cause elevated levels of pathological hallmarks such as amyloid-beta (Aβ). Although the genetics of Alzheimer's disease is well known, familial AD only accounts for a small number of cases in the population, with the rest being sporadic AD, which contains no known mutations...
April 17, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28416790/a-meta-analysis-of-cerebrospinal-fluid-visinin-like-protein-1-in-alzheimers-disease-patients-relative-to-healthy-controls-and-mild-cognitive-impairment-patients
#13
Xiaohui Hu, Yan Yang, Daokai Gong
OBJECTIVE: To compare cerebrospinal fluid visinin-like protein-1 (CSF VLP-1) in alzheimer`s disease (AD) with that in healthy controls and mild cognitive impairment (MCI) patients and find out possible sources of heterogeneity. METHODS: "Visinin-like protein-1" and "alzheimer`s disease" were employed to search "PubMed", "Springer" and "Medline" databases until July 2016 and standard mean difference (Std.MD) was calculated. Besides, subgroup analysis and meta-regression were performed to explore the possible heterogeneity sources...
April 2017: Neurosciences: the Official Journal of the Pan Arab Union of Neurological Sciences
https://www.readbyqxmd.com/read/28413821/cerebrospinal-fluid-biomarkers-for-alzheimer-s-disease-in-down-syndrome
#14
Alain D Dekker, Juan Fortea, Rafael Blesa, Peter P De Deyn
Down syndrome (DS), present in nearly six million people, is associated with an extremely high risk to develop Alzheimer's disease (AD). Amyloid-β and tau pathology are omnipresent from age 40 years onward, but clinical symptoms do not appear in all DS individuals. Dementia diagnostics is complex in this population, illustrating the great need for predictive biomarkers. Although blood biomarkers have not yet proven useful, cerebrospinal fluid (CSF) biomarkers (low amyloid-β42, high t-tau, and high p-tau) effectively contribute to AD diagnoses in the general population and are increasingly used in clinical practice...
2017: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/28404803/neuropsychiatric-symptoms-predict-hypometabolism-in-preclinical-alzheimer-disease
#15
Kok Pin Ng, Tharick A Pascoal, Sulantha Mathotaarachchi, Chang-Oh Chung, Andréa L Benedet, Monica Shin, Min Su Kang, Xiaofeng Li, Maowen Ba, Nagaendran Kandiah, Pedro Rosa-Neto, Serge Gauthier
OBJECTIVE: To identify regional brain metabolic dysfunctions associated with neuropsychiatric symptoms (NPS) in preclinical Alzheimer disease (AD). METHODS: We stratified 115 cognitively normal individuals into preclinical AD (both amyloid and tau pathologies present), asymptomatic at risk for AD (either amyloid or tau pathology present), or healthy controls (no amyloid or tau pathology present) using [(18)F]florbetapir PET and CSF phosphorylated tau biomarkers...
April 12, 2017: Neurology
https://www.readbyqxmd.com/read/28394917/a%C3%AE-levels-in-the-jugular-vein-and-high-molecular-weight-a%C3%AE-oligomer-levels-in-csf-can-be-used-as-biomarkers-to-indicate-the-anti-amyloid-effect-of-ivig-for-alzheimer-s-disease
#16
Takashi Kasai, Masaki Kondo, Ryotaro Ishii, Akihiro Tanaka, Suzuka Ataka, Hiroyuki Shimada, Takami Tomiyama, Hiroshi Mori, Mark Taylor, David Allsop, Masanori Nakagawa, Toshiki Mizuno, Takahiko Tokuda
Intravenous immunoglobulin (IVIg) has been a candidate as a potential anti-amyloid immunotherapy for Alzheimer disease (AD) because it contains anti-amyloid β (Aβ) antibodies. Although several studies with IVIg in AD have been published, changing levels of Aβ efflux from the brain, or disaggregation of Aβ species induced by immunotherapy, have not been properly investigated. Here, we carried out an open label study of therapy with IVIg in five patients with AD. We collected plasma from a peripheral vein (peripheral-plasma) and from the internal jugular vein (jugular-plasma) to estimate directly the efflux of soluble Aβ from the brain...
2017: PloS One
https://www.readbyqxmd.com/read/28393582/insights-into-the-human-brain-proteome-disclosing-the-biological-meaning-of-protein-networks-in-cerebrospinal-fluid
#17
Paulo Bastos, Rita Ferreira, Bruno Manadas, Paula I Moreira, Rui Vitorino
Cerebrospinal fluid (CSF) is an excellent source of biological information regarding the nervous system, once it is in close contact and accurately reflects alterations in this system. Several studies have analyzed differential protein profiles of CSF samples between healthy and diseased human subjects. However, the pathophysiological mechanisms and how CSF proteins relate to diseases are still poorly known. By applying bioinformatics tools, we attempted to provide new insights on the biological and functional meaning of proteomics data envisioning the identification of putative disease biomarkers...
April 10, 2017: Critical Reviews in Clinical Laboratory Sciences
https://www.readbyqxmd.com/read/28389645/enhanced-interstitial-fluid-drainage-in-the-hippocampus-of-spontaneously-hypertensive-rats
#18
Beatrice Bedussi, Daphne M P Naessens, Judith de Vos, Rik Olde Engberink, Micha M M Wilhelmus, Edo Richard, Malyssa Ten Hove, Ed vanBavel, Erik N T P Bakker
Hypertension is associated with cognitive decline and various forms of dementia, including Alzheimer's disease. In animal models of hypertension, many of Alzheimer's disease characteristics are recapitulated, including brain atrophy, cognitive decline, amyloid β accumulation and blood brain barrier dysfunction. Removal of amyloid β and other waste products depends in part on clearance via the brain interstitial fluid (ISF). Here we studied the impact of hypertension on ISF drainage, using spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY)...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28385104/prolonged-cerebrospinal-fluid-neurofilament-light-chain-increase-in-patients-with-post-traumatic-disorders-of-consciousness
#19
Sergio Bagnato, Luigi M E Grimaldi, Giorgio Di Raimondo, Antonino Sant'Angelo, Cristina Boccagni, Vittorio Virgilio, Maria Andriolo
The mechanisms involved in secondary brain injury after the acute phase of severe traumatic brain injury (TBI) are largely unknown. Ongoing axonal degeneration, consequent to the initial trauma, may lead to secondary brain injury. To test this hypothesis, we evaluated the cerebrospinal fluid (CSF) level of neurofilament light chain (NF-L), a proposed marker of axonal degeneration, in ten patients who developed a severe disorder of consciousness after a TBI, including seven in a minimally conscious state and three with unresponsive wakefulness syndrome (time since brain injury 309 ± 169 days)...
April 7, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28382304/tau-oligomers-in-cerebrospinal-fluid-in-alzheimer-s-disease
#20
Urmi Sengupta, Erik Portelius, Oskar Hansson, Kathleen Farmer, Diana Castillo-Carranza, Randall Woltjer, Henrik Zetterberg, Douglas Galasko, Kaj Blennow, Rakez Kayed
OBJECTIVE: With an increasing incidence of Alzheimer's disease (AD) and neurodegenerative tauopathies, there is an urgent need to develop reliable biomarkers for the diagnosis and monitoring of the disease, such as the recently discovered toxic tau oligomers. Here, we aimed to demonstrate the presence of tau oligomers in the cerebrospinal fluid (CSF) of patients with cognitive deficits, and to determine whether tau oligomers could serve as a potential biomarker for AD. METHODS: A multicentric collaborative study involving a double-blinded analysis with a total of 98 subjects with moderate to severe AD (N = 41), mild AD (N = 31), and nondemented control subjects (N = 26), and two pilot studies of 33 total patients with AD (N = 19) and control (N = 14) subjects were performed...
April 2017: Annals of Clinical and Translational Neurology
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