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CSF and Alzheimer

Maria Garranzo-Asensio, Pablo San Segundo-Acosta, Javier Martínez-Useros, Ana Montero-Calle, María Jesús Fernández-Aceñero, Anna Häggmark-Månberg, Alberto Pelaez-Garcia, Mayte Villalba, Alberto Rabano, Peter Nilsson, Rodrigo Barderas
Alzheimer's disease (AD) is the most common form of dementia in developed countries. A better understanding of the events taking place at the molecular level would help to identify novel protein alterations, which might be used in diagnosis or for treatment development. In this study, we have performed the high-throughput analysis of 706 molecules mostly implicated in cell-cell communication and cell signaling processes by using two antibody microarray platforms. We screened three AD pathological groups -each one containing four pooled samples- from Braak stages IV, V and VI, and three control groups from two healthy subjects, five frontotemporal and two vascular dementia patients onto Panorama and L-Series antibody microarrays to identify AD-specific alterations not common to other dementias...
February 16, 2018: Oncotarget
Elena Pérez-Ruiz, Deborah Decrop, Karen Ven, Lisa Tripodi, Karen Leirs, Joelle Rosseels, Marlies van de Wouwer, Nick Geukens, Ann De Vos, Eugeen Vanmechelen, Joris Winderickx, Jeroen Lammertyn, Dragana Spasic
The close correlation between Tau pathology and Alzheimer's disease (AD) progression makes this protein a suitable biomarker for diagnosis and monitoring of the disorder evolution. However, the use of Tau in diagnostics has been hampered, as it currently requires collection of cerebrospinal fluid (CSF), which is an invasive clinical procedure. Although measuring Tau-levels in blood plasma would be favorable, the concentrations are below the detection limit of a conventional ELISA. In this work, we developed a digital ELISA for the quantification of attomolar protein Tau concentrations in both buffer and biological samples...
July 26, 2018: Analytica Chimica Acta
Filipa Ladeira, Gonçalo Cação, Ana P Correia, Pedro S Pinto, Sara Cavaco, Manuel Melo-Pires, Isabel Alonso, Ricardo Taipa
No abstract text is available yet for this article.
March 9, 2018: Alzheimer Disease and Associated Disorders
Lena L Law, Rachael N Rol, Stephanie A Schultz, Ryan J Dougherty, Dorothy F Edwards, Rebecca L Koscik, Catherine L Gallagher, Cynthia M Carlsson, Barbara B Bendlin, Henrik Zetterberg, Kaj Blennow, Sanjay Asthana, Mark A Sager, Bruce P Hermann, Sterling C Johnson, Dane B Cook, Ozioma C Okonkwo
Introduction: Alzheimer's disease (AD) is characterized by the presence of amyloid β (Aβ) plaques, neurofibrillary tangles, and neurodegeneration, evidence of which may be detected in vivo via cerebrospinal fluid (CSF) sampling. Physical activity (PA) has emerged as a possible modifier of these AD-related pathological changes. Consequently, the aim of this study was to cross-sectionally examine the relationship between objectively measured PA and CSF levels of Aβ42 and tau in asymptomatic late-middle-aged adults at risk for AD...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Claudio Liguori, Mariangela Pierantozzi, Agostino Chiaravalloti, Giulia M Sancesario, Nicola B Mercuri, Flaminia Franchini, Orazio Schillaci, Giuseppe Sancesario
Late-life depression (LLD) and Alzheimer's Disease (AD) are the two most frequent neuropsychiatric disorders affecting elderly. LLD and AD may clinically present with depressive and cognitive symptoms. Therefore, when cognitive decline is coupled with depression in the elderly, the differential diagnosis between LLD and AD could be challenging. The aim of the present study was to evaluate in a population of elderly patients affected by depression and dementia the usefulness of CSF AD biomarkers (tau proteins and β-amyloid42 -Aβ42 ) and 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography (18FFDG-PET) in early differentiating LLD from AD...
2018: Frontiers in Aging Neuroscience
Lindsay R Clark, Sara E Berman, Derek Norton, Rebecca L Koscik, Erin Jonaitis, Kaj Blennow, Barbara B Bendlin, Sanjay Asthana, Sterling C Johnson, Henrik Zetterberg, Cynthia M Carlsson
OBJECTIVE: Compare cognitive and hippocampal volume trajectories in asymptomatic middle-aged and older adults with positive CSF markers of β-amyloid (Aβ) or tau to adults without an Alzheimer disease (AD)-associated biomarker profile. METHODS: Three hundred ninety-two adults enrolled in a longitudinal cohort study (Wisconsin Registry for Alzheimer's Prevention or Wisconsin Alzheimer's Disease Research Center) completed a lumbar puncture and at least 2 biennial or annual neuropsychological evaluations...
March 9, 2018: Neurology
Eline A J Willemse, Ann De Vos, Elizabeth M Herries, Ulf Andreasson, Sebastiaan Engelborghs, Wiesje M van der Flier, Philip Scheltens, Dan Crimmins, Jack H Ladenson, Eugeen Vanmechelen, Henrik Zetterberg, Anne M Fagan, Kaj Blennow, Maria Bjerke, Charlotte E Teunissen
BACKGROUND: Neurogranin in cerebrospinal fluid (CSF) correlates with cognitive decline and is a potential novel biomarker for Alzheimer disease (AD) dementia. We investigated the analytical and diagnostic performance of 3 commonly used neurogranin assays in the same cohort of patients to improve the interpretability of CSF neurogranin test results. METHODS: The neurogranin Singulex assay from Washington University, St. Louis, MO (WashU); ELISA from ADx Neurosciences; and ELISA from Gothenburg University, Mölndal, Sweden (UGot), were compared using silver staining and Western blot after gel electrophoresis...
March 9, 2018: Clinical Chemistry
Csaba Fekete, Csaba Vastagh, Ádám Dénes, Erik Hrabovszky, Gábor Nyiri, Imre Kalló, Zsolt Liposits, Miklós Sárvári
Microglia are instrumental for recognition and elimination of amyloid β1-42 oligomers (AβO), but the long-term consequences of AβO-induced inflammatory changes in the brain are unclear. Here, we explored microglial responses and transciptome-level inflammatory signatures in the rat hippocampus after chronic AβO challenge. Middle-aged Long Evans rats received intracerebroventricular infusion of AβO or vehicle for 4 weeks, followed by treatment with artificial CSF or MCC950 for the subsequent 4 weeks. AβO infusion evoked a sustained inflammatory response including activation of NF-κB, triggered microglia activation and increased the expression of pattern recognition and phagocytic receptors...
March 6, 2018: Neuroscience
J W Gause, R J Day, C A Caraway, W W Poon, T T Rohn
Recent studies have supported a role for the proteolytic cleavage of apolipoprotein E4 (APOE4) as a potential mechanism for the enhanced dementia risk associated with Alzheimer's disease. To determine whether APOE4 fragmentation is correlated with AD, ELISA assays were performed with cerebral spinal fluid (CSF) and plasma samples utilizing an antibody that specifically detects a 17 kDa amino-terminal fragment (p17) of APOE (nApoECF antibody). In CSF samples, levels of APOE fragmentation were minimal in both neuropathological normals (NPNs) and AD cases and there were no significant differences between the two cohorts across APOE genotypes...
September 2017: Journal of Neurology and Neurological Disorders
Petros Takousis
Changes associated with neurodegeneration at the cellular level are manifestations of deregulated biochemical pathways, and typically precede neuronal loss. Incorporation of molecular markers in the diagnostic process could aid detection of early changes, prior to extensive neuronal loss, as early as the presymptomatic stages of the disorder, thus enabling improved patient stratification for targeted drug development. Such biomarkers should be sufficiently sensitive and specific to distinguish AD from other disorders with overlapping symptoms...
2018: Methods in Molecular Biology
Carles Falcon, Grégory Operto, José Luis Molinuevo, Juan Domingo Gispert
Among others, the existence of pathophysiological biomarkers such as cerebrospinal fluid (CSF) Aβ-42, t-tau, and p-tau preceding the onset of Alzheimer's disease (AD) symptomatology have shifted the conceptualization of AD as a continuum. In addition, magnetic resonance imaging (MRI) enables the study of structural and functional cross-sectional correlates and longitudinal changes in vivo and, therefore, the combination of CSF data and imaging analyses emerges as a synergistic approach to understand the structural correlates related with specific AD-related biomarkers...
2018: Methods in Molecular Biology
Johannes Denk, Holger Jahn
MicroRNAs (miRNAs) are a class of small, highly conserved, and noncoding RNAs that modulate gene expression by regulating the activity and stability of target mRNAs. MiRNAs play significant roles by controlling fundamental cellular processes and its deregulation is associated with various diseases. Ubiquitous expression and its release into circulation make them interesting biomarkers, which can be measured by different platforms. In this book chapter, we provide a specific protocol that describes the detection of circulating miRNAs in CSF by using RT-qPCR...
2018: Methods in Molecular Biology
Angelo Palmigiano, Angela Messina, Rosaria Ornella Bua, Rita Barone, Luisa Sturiale, Mario Zappia, Domenico Garozzo
In this chapter, we present the methodology currently applied in our laboratory for the structural elucidation of the cerebrospinal fluid (CSF) N-glycome. N-glycans are released from denatured carboxymethylated glycoproteins by digestion with peptide-N-glycosidase F (PNGase F) and purified using both C18 Sep-Pak® and porous graphitized carbon (PGC) HyperSep™ Hypercarb™ solid-phase extraction (SPE) cartridges. The glycan pool is subsequently permethylated to increase mass spectrometry sensitivity. Molecular assignments are performed through matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS) analysis considering either the protein N-linked glycosylation pathway or MALDI TOF MS/MS data...
2018: Methods in Molecular Biology
Bianca A Trombetta, Becky C Carlyle, Aaron M Koenig, Leslie M Shaw, John Q Trojanowski, David A Wolk, Joseph J Locascio, Steven E Arnold
OBJECTIVE: Alzheimer's disease (AD) is a complex neurodegenerative disease driven by multiple interacting pathophysiological processes that ultimately results in synaptic loss, neuronal death, and dementia. We implemented a fit-for-purpose modeled approach to qualify a broad selection of commercially available immunoassays and evaluate the biotemporal stability of analytes across five pathophysiological domains of interest in AD, including core amyloid-β (Aβ) and tau AD biomarkers, neurodegeneration, inflammation/immune modulation, neurovascular injury, and metabolism/oxidative stress...
2018: PloS One
Roberta Ghidoni, Rosanna Squitti, Mariacristina Siotto, Luisa Benussi
The criteria for the clinical diagnosis of AD include the analysis of biomarkers of the underlying brain disease pathology; a set of cerebrospinal fluid (CSF) tests, amyloid-β1-42 (Aβ42), total-tau (t-tau), and phosphorylated tau (p-tau), are available and their performance in a clinical setting has been assessed in several studies. Thus, in dementia research, great advances have been made in the discovery of putative biomarkers; however, disappointingly, few of them have been translated into clinically applicable assays...
February 28, 2018: Journal of Alzheimer's Disease: JAD
Lisa Flem Kalheim, Tormod Fladby, Christopher Coello, Atle Bjrnerud, Per Selnes
Flutemetamol (18F-Flut) is an [18F]-labelled amyloid PET tracer with increasing availability. The main objectives of this study were to investigate 1) cerebrospinal fluid (CSF) Aβ 1-42 (Aβ42) concentrations associated with regional 18F-Flut uptake, 2) associations between cortical 18F-Flut and [18F]-fludeoxyglucose (18F-FDG)-PET, and 3) the potential use of 18F-Flut in WM pathology. Cognitively impaired, nondemented subjects were recruited (n = 44). CSF was drawn, and 18F-Flut-PET, 18F-FDG-PET, and MRI performed...
March 1, 2018: Journal of Alzheimer's Disease: JAD
Suzanne E Schindler, Julia D Gray, Brian A Gordon, Chengjie Xiong, Richard Batrla-Utermann, Marian Quan, Simone Wahl, Tammie L S Benzinger, David M Holtzman, John C Morris, Anne M Fagan
INTRODUCTION: Levels of amyloid β peptide 42 (Aβ42), total tau, and phosphorylated tau-181 are well-established cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease, but variability in manual plate-based assays has limited their use. We examined the relationship between CSF biomarkers, as measured by a novel automated immunoassay platform, and amyloid positron emission tomography. METHODS: CSF samples from 200 individuals underwent separate analysis for Aβ42, total tau, and phosphorylated tau-181 with the automated Roche Elecsys cobas e 601 analyzer...
March 1, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Bruno Dubois, Stephane Epelbaum, Francis Nyasse, Hovagim Bakardjian, Geoffroy Gagliardi, Olga Uspenskaya, Marion Houot, Simone Lista, Federica Cacciamani, Marie-Claude Potier, Anne Bertrand, Foudil Lamari, Habib Benali, Jean-François Mangin, Olivier Colliot, Remy Genthon, Marie-Odile Habert, Harald Hampel
BACKGROUND: Improved understanding is needed of risk factors and markers of disease progression in preclinical Alzheimer's disease. We assessed associations between brain β-amyloidosis and various cognitive and neuroimaging parameters with progression of cognitive decline in individuals with preclinical Alzheimer's disease. METHODS: The INSIGHT-preAD is an ongoing single-centre observational study at the Salpêtrière Hospital, Paris, France. Eligible participants were age 70-85 years with subjective memory complaints but unimpaired cognition and memory (Mini-Mental State Examination [MMSE] score ≥27, Clinical Dementia Rating score 0, and Free and Cued Selective Reminding Test [FCSRT] total recall score ≥41)...
February 27, 2018: Lancet Neurology
Oskar Hansson, John Seibyl, Erik Stomrud, Henrik Zetterberg, John Q Trojanowski, Tobias Bittner, Valeria Lifke, Veronika Corradini, Udo Eichenlaub, Richard Batrla, Katharina Buck, Katharina Zink, Christina Rabe, Kaj Blennow, Leslie M Shaw
INTRODUCTION: We studied whether fully automated Elecsys cerebrospinal fluid (CSF) immunoassay results were concordant with PET and predicted clinical progression, even with cutoffs established in an independent cohort. METHODS: Cutoffs for Elecsys amyloid-β1-42 (Aβ), total tau/Aβ(1-42), and phosphorylated tau/Aβ(1-42) were defined against [18 F]flutemetamol PET in Swedish BioFINDER (n = 277) and validated against [18 F]florbetapir PET in Alzheimer's Disease Neuroimaging Initiative (n = 646)...
February 27, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Francesc X Guix, Grant T Corbett, Diana J Cha, Maja Mustapic, Wen Liu, David Mengel, Zhicheng Chen, Elena Aikawa, Tracy Young-Pearse, Dimitrios Kapogiannis, Dennis J Selkoe, Dominic M Walsh
Progressive cerebral accumulation of tau aggregates is a defining feature of Alzheimer's disease (AD). A popular theory that seeks to explain the apparent spread of neurofibrillary tangle pathology proposes that aggregated tau is passed from neuron to neuron. Such a templated seeding process requires that the transferred tau contains the microtubule binding repeat domains that are necessary for aggregation. While it is not clear how a protein such as tau can move from cell to cell, previous reports have suggested that this may involve extracellular vesicles (EVs)...
February 27, 2018: International Journal of Molecular Sciences
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