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CSF and Alzheimer

Jia Cheng, XiaoFeng Guo, Tian Zhang, Li Zhong, GuoJun Bu, XiaoFen Chen
Triggering receptor expressed on myeloid cells (TREMs) receptors constitute a family modulators in human innate immunity system that encode by a gene cluster. Rare variants in TREM2 were reported to be associated with significant Alzheimer's disease (AD) risk. However, inconsistent results were also reported in some studies of Non-European descents. Recently, the other TREM family members are also considered to involve in AD and cerebrospinal fluid (CSF) soluble form of TREM2 (sTREM2) levels has also been associated with respond to progression of disease...
October 18, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
Dennis Chan, Laura Marie Gallaher, Kuven Moodley, Ludovico Minati, Neil Burgess, Tom Hartley
This protocol describes the administration of the 4 Mountains Test (4MT), a short test of spatial memory, in which memory for the topographical layout of four mountains within a computer-generated landscape is tested using a delayed match-to-sample paradigm. Allocentric spatial memory is assessed by altering the viewpoint, colors and textures between the initially presented and target images. Allocentric spatial memory is a key function of the hippocampus, one of the earliest brain regions to be affected in Alzheimer's disease (AD) and impairment of hippocampal function predates the onset of dementia...
October 13, 2016: Journal of Visualized Experiments: JoVE
Rui Gao, Guangjian Zhang, Xueqi Chen, Aimin Yang, Gwenn Smith, Dean F Wong, Yun Zhou
OBJECTIVE: Cerebrospinal fluid (CSF) biomarkers, such as α-synuclein (α-syn), amyloid beta peptide 1-42 (Aβ1-42), phosphorylated tau (181P) (p-tau), and total tau (t-tau), have long been associated with the development of Parkinson disease (PD) and other neurodegenerative diseases. In this investigation, we reported the assessment of CSF biomarkers and their correlations with vesicular monoamine transporter 2 (VMAT2) bindings measured with 18F-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-AV133) that is being developed as a biomarker for PD...
2016: PloS One
Carlo Wilke, Frank Gillardon, Christian Deuschle, Markus A Hobert, Iris E Jansen, Florian G Metzger, Peter Heutink, Thomas Gasser, Walter Maetzler, Cornelis Blauwendraat, Matthis Synofzik
BACKGROUND AND OBJECTIVE: Reduced progranulin levels are a hallmark of frontotemporal dementia (FTD) caused by loss-of-function (LoF) mutations in the progranulin gene (GRN). However, alterations of central nervous progranulin expression also occur in neurodegenerative disorders unrelated to GRN mutations, such as Alzheimer's disease. We hypothesised that central nervous progranulin levels are also reduced in GRN-negative FTD. METHODS: Progranulin levels were determined in both cerebrospinal fluid (CSF) and serum in 75 subjects (37 FTD patients and 38 controls)...
October 20, 2016: Neuro-degenerative Diseases
Tomoyuki Masuda, Junko Itoh, Takuya Koide, Yasushi Tomidokoro, Yosuke Takei, Kazuhiro Ishii, Akira Tamaoka
A chronic inflammatory condition may underlie neurodegenerative disorders, including Parkinson's disease (PD) and Alzheimer's disease (AD). For example, both PD and AD patients show an increase in transforming growth factor-β1 (TGF-β1) levels in their cerebrospinal fluid (CSF). TGF-β1 is a cytokine that inhibits inflammation. In the present study, using an enzyme-linked immunosorbent assay, we tested the hypothesis that the level of TGF-β1 in the CSF of patients with amyotrophic lateral sclerosis (ALS), spinocerebellar degeneration (SCD), or multiple system atrophy-cerebellar subtype (MSA-C) would be elevated compared with that of normal controls...
October 15, 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Graham Fairfoul, Lynne I McGuire, Suvankar Pal, James W Ironside, Juliane Neumann, Sharon Christie, Catherine Joachim, Margaret Esiri, Samuel G Evetts, Michal Rolinski, Fahd Baig, Claudio Ruffmann, Richard Wade-Martins, Michele T M Hu, Laura Parkkinen, Alison J E Green
We have developed a novel real-time quaking-induced conversion RT-QuIC-based assay to detect alpha-synuclein aggregation in brain and cerebrospinal fluid from dementia with Lewy bodies and Parkinson's disease patients. This assay can detect alpha-synuclein aggregation in Dementia with Lewy bodies and Parkinson's disease cerebrospinal fluid with sensitivities of 92% and 95%, respectively, and with an overall specificity of 100% when compared to Alzheimer and control cerebrospinal fluid. Patients with neuropathologically confirmed tauopathies (progressive supranuclear palsy; corticobasal degeneration) gave negative results...
October 2016: Annals of Clinical and Translational Neurology
Juliane Schelle, Lisa Häsler, Jens C Göpfert, Thomas O Joos, Hugo Vanderstichele, Erik Stoops, Ulf Neumann, Derya R Shimshek, Matthias Staufenbiel, Mathias Jucker, Stephan A Kaeser
INTRODUCTION: The inhibition of the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is a main therapeutic approach for the treatment of Alzheimer's disease (AD). We previously reported an age-related increase of tau protein in the cerebrospinal fluid (CSF) of Aβ precursor protein (APP) transgenic mice. METHODS: APP transgenic mice were treated with a potent BACE1 inhibitor. CSF tau and CSF Aβ levels were assessed. A novel high-sensitivity tau sandwich immunoassay was developed...
October 14, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Antti J Luikku, Anette Hall, Ossi Nerg, Anne M Koivisto, Mikko Hiltunen, Seppo Helisalmi, Sanna-Kaisa Herukka, Anna Sutela, Maria Kojoukhova, Jussi Mattila, Jyrki Lötjönen, Jaana Rummukainen, Irina Alafuzoff, Juha E Jääskeläinen, Anne M Remes, Hilkka Soininen, Ville Leinonen
OBJECTIVES: Optimal selection of idiopathic normal pressure hydrocephalus (iNPH) patients for shunt surgery is challenging. Disease State Index (DSI) is a statistical method that merges multimodal data to assist clinical decision-making. It has previously been shown to be useful in predicting progression in mild cognitive impairment and differentiating Alzheimer's disease (AD) and frontotemporal dementia. In this study, we use the DSI method to predict shunt surgery response for patients with iNPH...
October 14, 2016: Acta Neurochirurgica
Ashvini Keshavan, Amanda Heslegrave, Henrik Zetterberg, Jonathan M Schott
Biomarkers in Alzheimer's disease (AD) have the potential to allow early and more accurate diagnosis, predict disease progression, stratify individuals and track response to candidate therapies in drug trials. The first fluid biomarkers reflecting aspects of AD neuropathology were identified in cerebrospinal fluid (CSF) in the 1990s. Three CSF biomarkers (amyloid-β 1-42, total tau and phospho-tau) have consistently been shown to have diagnostic utility and are incorporated into the new diagnostic criteria for AD...
October 13, 2016: Molecular Diagnosis & Therapy
Scott E Counts, Milos D Ikonomovic, Natosha Mercado, Irving E Vega, Elliott J Mufson
The recent failures of potential disease-modifying drugs for Alzheimer's disease (AD) may reflect the fact that the enrolled participants in clinical trials are already too advanced to derive a clinical benefit. Thus, well-validated biomarkers for the early detection and accurate diagnosis of the preclinical stages of AD will be crucial for therapeutic advancement. The combinatorial use of biomarkers derived from biological fluids, such as cerebrospinal fluid (CSF), with advanced molecular imaging and neuropsychological testing may eventually achieve the diagnostic sensitivity and specificity necessary to identify people in the earliest stages of the disease when drug modification is most likely possible...
October 13, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Adrià Dangla-Valls, José Luis Molinuevo, Jordi Altirriba, Raquel Sánchez-Valle, Daniel Alcolea, Juan Fortea, Lorena Rami, Mircea Balasa, Cristina Muñoz-García, Mario Ezquerra, Rubén Fernández-Santiago, Alberto Lleó, Albert Lladó, Anna Antonell
MicroRNAs (miRNAs) are short non-coding RNA molecules that regulate gene expression through post-transcriptional repression of target genes. They have been shown to be implicated in the pathophysiology of Alzheimer's disease (AD) and proposed as disease biomarkers. In the present work, we have studied the expression levels of 754 miRNAs in cerebrospinal fluid (CSF) from AD patients and control subjects. We have explored a first screening cohort (N = 20) and selected 12 miRNAs to be further tested in a second independent validation cohort (N = 69)...
October 13, 2016: Molecular Neurobiology
Matthias Schmitz, Maria Cramm, Franc Llorens, Dominik Müller-Cramm, Steven Collins, Ryuichiro Atarashi, Katsuya Satoh, Christina D Orrù, Bradley R Groveman, Saima Zafar, Walter J Schulz-Schaeffer, Byron Caughey, Inga Zerr
The development and adaption of in vitro misfolded protein amplification systems has been a major innovation in the detection of abnormally folded prion protein scrapie (PrP(Sc)) in human brain and cerebrospinal fluid (CSF) samples. Herein, we describe a fast and efficient protein amplification technique, real-time quaking-induced conversion (RT-QuIC), for the detection of a PrP(Sc) seed in human brain and CSF. In contrast to other in vitro misfolded protein amplification assays-such as protein misfolding cyclic amplification (PMCA)-which are based on sonication, the RT-QuIC technique is based on prion seed-induced misfolding and aggregation of recombinant prion protein substrate, accelerated by alternating cycles of shaking and rest in fluorescence plate readers...
November 2016: Nature Protocols
Farron L McIntee, Patrizia Giannoni, Steven Blais, George Sommer, Thomas A Neubert, Agueda Rostagno, Jorge Ghiso
Amyloid β (Aβ) is the major constituent of the brain deposits found in parenchymal plaques and cerebral blood vessels of patients with Alzheimer's disease (AD). Several lines of investigation support the notion that synaptic pathology, one of the strongest correlates to cognitive impairment, is related to the progressive accumulation of neurotoxic Aβ oligomers. Since the process of oligomerization/fibrillization is concentration-dependent, it is highly reliant on the homeostatic mechanisms that regulate the steady state levels of Aβ influencing the delicate balance between rate of synthesis, dynamics of aggregation, and clearance kinetics...
2016: Frontiers in Aging Neuroscience
Amado Rivero-Santana, Daniel Ferreira, Lilisbeth Perestelo-Pérez, Eric Westman, Lars-Olof Wahlund, Antonio Sarría, Pedro Serrano-Aguilar
BACKGROUND: Differential diagnosis in dementia is at present one of the main challenges both in clinical practice and research. Cerebrospinal fluid (CSF) biomarkers are included in the current diagnostic criteria of Alzheimer's disease (AD) but their clinical utility is still unclear. OBJECTIVE: We performed a systematic review of studies analyzing the diagnostic performance of CSF Aβ42, total tau (t-tau), and phosphorylated tau (p-tau) in the discrimination between AD and frontotemporal lobar degeneration (FTLD) dementias...
October 4, 2016: Journal of Alzheimer's Disease: JAD
Martina Pigoni, Johanna Wanngren, Peer-Hendrik Kuhn, Kathryn M Munro, Jenny M Gunnersen, Hiroshi Takeshima, Regina Feederle, Iryna Voytyuk, Bart De Strooper, Mikail D Levasseur, Brian J Hrupka, Stephan A Müller, Stefan F Lichtenthaler
BACKGROUND: The protease BACE1 (beta-site APP cleaving enzyme) is a major drug target in Alzheimer's disease. However, BACE1 therapeutic inhibition may cause unwanted adverse effects due to its additional functions in the nervous system, such as in myelination and neuronal connectivity. Additionally, recent proteomic studies investigating BACE1 inhibition in cell lines and cultured murine neurons identified a wider range of neuronal membrane proteins as potential BACE1 substrates, including seizure protein 6 (SEZ6) and its homolog SEZ6L...
October 5, 2016: Molecular Neurodegeneration
Annika Öhrfelt, Ann Brinkmalm, Julien Dumurgier, Gunnar Brinkmalm, Oskar Hansson, Henrik Zetterberg, Elodie Bouaziz-Amar, Jacques Hugon, Claire Paquet, Kaj Blennow
BACKGROUND: Synaptic degeneration is a central pathogenic event in Alzheimer's disease that occurs early during the course of disease and correlates with cognitive symptoms. The pre-synaptic vesicle protein synaptotagmin-1 appears to be essential for the maintenance of an intact synaptic transmission and cognitive function. Synaptotagmin-1 in cerebrospinal fluid is a candidate Alzheimer biomarker for synaptic dysfunction that also may correlate with cognitive decline. METHODS: In this study, a novel mass spectrometry-based assay for measurement of cerebrospinal fluid synaptotagmin-1 was developed, and was evaluated in two independent sample sets of patients and controls...
October 3, 2016: Alzheimer's Research & Therapy
Xiao Luo, Tiantian Qiu, Yunlu Jia, Peiyu Huang, Xiaojun Xu, Xinfeng Yu, Zhujing Shen, Yerfan Jiaerken, Xiaojun Guan, Jiong Zhou, Minming Zhang
Apolipoprotein E (APOE) ε4 allele is the best established genetic risk factor for sporadic Alzheimer's disease (AD). However, there is a need to understand the effects of this genotype on the brain by simultaneously assessing intrinsic brain network and cerebral spinal fluid (CSF) biomarkers changes in healthy older ε4 carriers. Thirteen cognitively intact, elderly APOE ε4 carriers and 22 ε3 homozygotes were included in the present study. Eigenvector centrality mapping (ECM) was used to identify brain network hub organization based on resting-state functional MRI (rsfMRI)...
October 6, 2016: Brain Imaging and Behavior
Cheng-Chun Wu, I-Fang Wang, Po-Min Chiang, Liang-Chao Wang, Che-Kun James Shen, Kuen-Jer Tsai
Recent studies reported granulocyte colony-stimulating factor (G-CSF) treatment can improve the cognitive function of Alzheimer's disease (AD) mice, and the mobilized hematopoietic stem cells (HSCs) or bone marrow mesenchymal stem cells (BM-MSCs) are proposed to be involved in this recovery effect. However, the exact role of mobilized HSC/BM-MSC in G-CSF-based therapeutic effects is still unknown. Here, we report that C-X-C chemokine receptor type 4 (CXCR4)/stromal cell-derived factor 1 (SDF-1) chemotaxis was a key mediator in G-CSF-based therapeutic effects, which was involved in the recruitment of repair-competent cells...
October 5, 2016: Molecular Neurobiology
Niklas Mattsson, Henrik Zetterberg, Shorena Janelidze, Philip S Insel, Ulf Andreasson, Erik Stomrud, Sebastian Palmqvist, David Baker, Cristina A Tan Hehir, Andreas Jeromin, David Hanlon, Linan Song, Leslie M Shaw, John Q Trojanowski, Michael W Weiner, Oskar Hansson, Kaj Blennow
OBJECTIVE: To test whether plasma tau is altered in Alzheimer disease (AD) and whether it is related to changes in cognition, CSF biomarkers of AD pathology (including β-amyloid [Aβ] and tau), brain atrophy, and brain metabolism. METHODS: This was a study of plasma tau in prospectively followed patients with AD (n = 179), patients with mild cognitive impairment (n = 195), and cognitive healthy controls (n = 189) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and cross-sectionally studied patients with AD (n = 61), mild cognitive impairment (n = 212), and subjective cognitive decline (n = 174) and controls (n = 274) from the Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study at Lund University, Sweden...
September 30, 2016: Neurology
Jordi Pegueroles, Eduard Vilaplana, Victor Montal, Frederic Sampedro, Daniel Alcolea, Maria Carmona-Iragui, Jordi Clarimon, Rafael Blesa, Alberto Lleó, Juan Fortea
BACKGROUND: Brain structural changes in preclinical Alzheimer's disease (AD) are poorly understood. METHODS: We compared the changes in cortical thickness in the ADNI cohort during a 2-year follow-up between the NIA-AA preclinical AD stages defined by cerebrospinal fluid (CSF) biomarker levels. We also analyzed the correlation between baseline CSF biomarkers and cortical atrophy rates. RESULTS: At follow-up, stage 1 subjects showed reduced atrophy rates in medial frontal areas compared to stage 0 subjects, whereas stage 2/3 subjects presented accelerated atrophy in medial temporal structures...
September 28, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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