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https://www.readbyqxmd.com/read/29776894/amyloid-pet-in-neurodegenerative-diseases-with-dementia
#1
V Camacho, A Gómez-Grande, P Sopena, D García-Solís, M Gómez Río, C Lorenzo, S Rubí, J Arbizu
Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive decline and memory loss, and is the most common form of dementia. Amyloid plaques with neurofibrillary tangles are a neuropathological hallmark of AD that produces synaptic dysfunction and culminates later in neuronal loss. Amyloid PET is a useful, available and non-invasive technique that provides in vivo information about the cortical amyloid burden. In the latest revised criteria for the diagnosis of AD biomarkers were defined and integrated: pathological and diagnostic biomarkers (increased retention on fibrillar amyloid PET or decreased Aβ1-42 and increased T-Tau or P-Tau in CSF) and neurodegeneration or topographical biomarkers (temporoparietal hypometabolism on 18 F-FDG PET and temporal atrophy on MRI)...
May 15, 2018: Revista Española de Medicina Nuclear e Imagen Molecular
https://www.readbyqxmd.com/read/29760644/an-algorithm-for-preclinical-diagnosis-of-alzheimer-s-disease
#2
REVIEW
Tapan K Khan
Almost all Alzheimer's disease (AD) therapeutic trials have failed in recent years. One of the main reasons for failure is due to designing the disease-modifying clinical trials at the advanced stage of the disease when irreversible brain damage has already occurred. Diagnosis of the preclinical stage of AD and therapeutic intervention at this phase, with a perfect target, are key points to slowing the progression of the disease. Various AD biomarkers hold enormous promise for identifying individuals with preclinical AD and predicting the development of AD dementia in the future, but no single AD biomarker has the capability to distinguish the AD preclinical stage...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29758941/from-cerebrospinal-fluid-to-blood-the-third-wave-of-fluid-biomarkers-for-alzheimer-s-disease
#3
Henrik Zetterberg, Kaj Blennow
The past five years have seen an enormous development in the field of fluid biomarkers for Alzheimer's disease (AD) and related disorders. The proteins that constitute the foundation for the cerebrospinal fluid (CSF) tests for the classical AD pathologies are now being explored as potential blood-based biomarkers, thanks to the recent implementation of ultrasensitive measurement technologies in academic and clinical laboratories worldwide. The current blood-derived data are still less clear than those obtained using CSF as the sample type, but independent research suggests that there are biomarker signals in blood that relate to plaque and tangle pathologies in AD, which are relevant to explore further...
May 11, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29754206/convective-influx-glymphatic-system-tracers-injected-into-the-csf-enter-and-leave-the-brain-along-separate-periarterial-basement-membrane-pathways
#4
Nazira J Albargothy, David A Johnston, Matthew MacGregor-Sharp, Roy O Weller, Ajay Verma, Cheryl A Hawkes, Roxana O Carare
Tracers injected into CSF pass into the brain alongside arteries and out again. This has been recently termed the "glymphatic system" that proposes tracers enter the brain along periarterial "spaces" and leave the brain along the walls of veins. The object of the present study is to test the hypothesis that: (1) tracers from the CSF enter the cerebral cortex along pial-glial basement membranes as there are no perivascular "spaces" around cortical arteries, (2) tracers leave the brain along smooth muscle cell basement membranes that form the Intramural Peri-Arterial Drainage (IPAD) pathways for the elimination of interstitial fluid and solutes from the brain...
May 12, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29751835/genome-wide-association-study-identified-atp6v1h-locus-influencing-cerebrospinal-fluid-bace-activity
#5
Hao Hu, Haiyan Li, Jieqiong Li, Jintai Yu, Lan Tan
BACKGROUND: The activity of cerebrospinal fluid (CSF) β-site APP cleaving enzyme (BACE) is a potential diagnostic biomarker for Alzheimer disease (AD). METHODS: A total of 340 non-Hispanic Caucasian participants from the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI) database were included in this study with quality-controlled CSF BACE and genotype data. Association of CSF BACE with the genetic variants of single nucleotide polymorphisms (SNPs) was assessed using PLINK under the additive genetic model...
May 11, 2018: BMC Medical Genetics
https://www.readbyqxmd.com/read/29746584/specific-serum-and-csf-microrna-profiles-distinguish-sporadic-behavioural-variant-of-frontotemporal-dementia-compared-with-alzheimer-patients-and-cognitively-healthy-controls
#6
Johannes Denk, Felix Oberhauser, Johannes Kornhuber, Jens Wiltfang, Klaus Fassbender, Matthias L Schroeter, Alexander E Volk, Janine Diehl-Schmid, Johannes Prudlo, Adrian Danek, Bernhard Landwehrmeyer, Martin Lauer, Markus Otto, Holger Jahn
Information on circulating miRNAs in frontotemporal lobar degeneration is very limited and conflicting results have complicated an interpretation in Alzheimer's disease thus far. In the present study we I) collected samples from multiple clinical centers across Germany, II) defined 3 homogenous patient groups with high sample sizes (bvFTD n = 48, AD n = 48 and cognitively healthy controls n = 44), III) compared expression levels in both CSF and serum samples and IV) detected a limited set of miRNAs by using a MIQE compliant protocol based on SYBR-green miRCURY assays that have proven reliable to generate reproducible results...
2018: PloS One
https://www.readbyqxmd.com/read/29741401/comparison-of-%C3%AE-2-microglobulin-serum-level-between-alzheimer-s-patients-cognitive-healthy-and-mild-cognitive-impaired-individuals
#7
Roberto Dominici, Dario Finazzi, Letizia Polito, Emanuela Oldoni, Giovanna Bugari, Alessandro Montanelli, Elio Scarpini, Daniela Galimberti, Antonio Guaita
BACKGROUND: Several studies performed in the last years on the brain, showed that beta2-microglobulin (β2m) and MHC can act independently of their canonical immune function to regulate normal brain development, synaptic plasticity and behaviour. Increased systemic levels of soluble β2m have been implicated in cognitive impairments like that associated with chronic hemodialysis, or aortic valve replacement. Increased soluble β2m has also been detected in the cerebral spinal fluid (CSF) of patients with HIV-associated dementia and Alzheimer's disease...
May 9, 2018: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/29740431/omics-based-approach-reveals-complement-mediated-inflammation-in-chronic-lymphocytic-inflammation-with-pontine-perivascular-enhancement-responsive-to-steroids-clippers
#8
Morten Blaabjerg, Anne Louise Hemdrup, Lylia Drici, Klemens Ruprecht, Peter Garred, Romana Höftberger, Bjarne W Kristensen, Daniel Kondziella, Tobias Sejbaek, Soren W Hansen, Helle H Nielsen, Pia Jensen, Morten Meyer, Friedemann Paul, Hans Lassmann, Martin R Larsen, Zsolt Illes
Objective: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare syndrome with relapsing brainstem/cerebellar symptoms. To examine the pathogenic processes and investigate potential biomarkers, we analyzed combined materials of brain and cerebrospinal fluid (CSF) by comprehensive methodologies. Materials and methods: To identify major pathways of perivascular inflammation in CLIPPERS, we first compared the CSF proteome ( n  = 5) to a neurodegenerative condition, Alzheimer's disease (AD, n  = 5)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29738432/neuroimmunology-research-a-report-from-the-cuban-network-of-neuroimmunology
#9
María de Los Angeles Robinson-Agramonte, Lourdes Lorigados Pedre, Orlando Ramón Serrano-Barrera
Neuroimmunology can be traced back to the XIX century through the descriptions of some of the disease’s models (e.g., multiple sclerosis and Guillain Barret syndrome, amongst others). The diagnostic tools are based in the cerebrospinal fluid (CSF) analysis developed by Quincke or in the development of neuroimmunotherapy with the earlier expression in Pasteur’s vaccine for rabies. Nevertheless, this field, which began to become delineated as an independent research area in the 1940s, has evolved as an innovative and integrative field at the shared edges of neurosciences, immunology, and related clinical and research areas, which are currently becoming a major concern for neuroscience and indeed for all of the scientific community linked to it...
May 8, 2018: Behavioral Sciences
https://www.readbyqxmd.com/read/29736986/identification-of-alzheimer-s-disease-and-mild-cognitive-impairment-using-multimodal-sparse-hierarchical-extreme-learning-machine
#10
Jongin Kim, Boreom Lee
Different modalities such as structural MRI, FDG-PET, and CSF have complementary information, which is likely to be very useful for diagnosis of AD and MCI. Therefore, it is possible to develop a more effective and accurate AD/MCI automatic diagnosis method by integrating complementary information of different modalities. In this paper, we propose multi-modal sparse hierarchical extreme leaning machine (MSH-ELM). We used volume and mean intensity extracted from 93 regions of interest (ROIs) as features of MRI and FDG-PET, respectively, and used p-tau, t-tau, and Aβ42 as CSF features...
May 7, 2018: Human Brain Mapping
https://www.readbyqxmd.com/read/29713273/targeting-beta-amyloid-at-the-csf-a-new-therapeutic-strategy-in-alzheimer-s-disease
#11
Manuel Menendez-Gonzalez, Huber S Padilla-Zambrano, Gabriel Alvarez, Estibaliz Capetillo-Zarate, Cristina Tomas-Zapico, Agustin Costa
Although immunotherapies against the amyloid-β (Aβ) peptide tried so date failed to prove sufficient clinical benefit, Aβ still remains the main target in Alzheimer's disease (AD). This article aims to show the rationale of a new therapeutic strategy: clearing Aβ from the CSF continuously (the "CSF-sink" therapeutic strategy). First, we describe the physiologic mechanisms of Aβ clearance and the resulting AD pathology when these mechanisms are altered. Then, we review the experiences with peripheral Aβ-immunotherapy and discuss the related hypothesis of the mechanism of action of "peripheral sink...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29710713/rapidly-progressive-alzheimer-s-disease-contributions-to-clinical-pathological-definition-and-diagnosis
#12
Samir Abu-Rumeileh, Sabina Capellari, Piero Parchi
Rapidly progressive Alzheimer's disease (rpAD) has recently been recognized as a clinical disease subtype characterized by rapidly progressive cognitive decline and/or short disease duration, and the possible occurrence of early focal neurological signs. Consistently, rpAD represents a relatively frequent alternative diagnosis among cases referred as possible or probable Creutzfeldt-Jakob disease (CJD) to surveillance centers for prion disease worldwide. Indeed, the early clinical differential diagnosis between the two disorders can be challenging given the partial overlap in clinical features and cerebrospinal fluid (CSF) levels of the protein surrogate markers 14-3-3 and total-tau...
April 25, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29706146/neuropsychological-profiles-and-trajectories-in-preclinical-alzheimer-s-disease
#13
Jean K Ho, Daniel A Nation
OBJECTIVES: The present study investigated the independent and synergistic effects of amyloid beta (Aβ1-42) and phosphorylated tau (Ptau) pathologies on neuropsychological profiles and trajectories in cognitively normal older adults. METHODS: Alzheimer's Disease Neuroimaging Initiative participants identified as cognitively normal at baseline underwent longitudinal assessment (N=518; 0, 12, 24, 36 months), baseline lumbar puncture and follow-up cognitive exams...
April 30, 2018: Journal of the International Neuropsychological Society: JINS
https://www.readbyqxmd.com/read/29700775/somatostatin-maintains-permeability-and-integrity-of-blood-brain-barrier-in-%C3%AE-amyloid-induced-toxicity
#14
Seungil Paik, Rishi K Somvanshi, Ujendra Kumar
In Alzheimer's disease (AD), the impaired clearance of β-amyloid peptide (Aβ) due to disrupted tight junction and transporter proteins is the prominent cause of disease progression. Somatostatin (SST) blocks the aggregation of Aβ and inflammation whereas reduction of SST levels in the CSF and brain tissue is associated with impaired cognitive function and memory loss. However, the role of SST in preservation of blood-brain barrier (BBB) integrity and functionality in Aβ-induced toxicity is not known. In the present study using human CMEC/D3 cells, we demonstrate that SST prevents Aβ-induced BBB permeability by regulating LRP1 and RAGE expression and improving the disrupted tight junction proteins...
April 26, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29700597/cerebrospinal-fluid-neurogranin-concentration-in-neurodegeneration-relation-to-clinical-phenotypes-and-neuropathology
#15
Erik Portelius, Bob Olsson, Kina Höglund, Nicholas C Cullen, Hlin Kvartsberg, Ulf Andreasson, Henrik Zetterberg, Åsa Sandelius, Leslie M Shaw, Virginia M Y Lee, David J Irwin, Murray Grossman, Daniel Weintraub, Alice Chen-Plotkin, David A Wolk, Leo McCluskey, Lauren Elman, Jennifer McBride, Jon B Toledo, John Q Trojanowski, Kaj Blennow
Neurogranin (Ng) is a post-synaptic protein that previously has been shown to be a biomarker for synaptic function when measured in cerebrospinal fluid (CSF). The CSF concentration of Ng is increased in Alzheimer's disease dementia (ADD), and even in the pre-dementia stage. In this prospective study, we used an enzyme-linked immunosorbent assay that quantifies Ng in CSF to test the performance of Ng as a marker of synaptic function. In 915 patients, CSF Ng was evaluated across several different neurodegenerative diseases...
April 26, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29695589/abby-a-phase-2-randomized-trial-of-crenezumab-in-mild-to-moderate-alzheimer-disease
#16
Jeffrey L Cummings, Sharon Cohen, Christopher H van Dyck, Mark Brody, Craig Curtis, William Cho, Michael Ward, Michel Friesenhahn, Christina Rabe, Flavia Brunstein, Angelica Quartino, Lee A Honigberg, Reina N Fuji, David Clayton, Deborah Mortensen, Carole Ho, Robert Paul
OBJECTIVE: To evaluate the safety and efficacy of crenezumab in patients with mild to moderate Alzheimer disease (AD). METHODS: In this phase 2 trial, 431 patients with mild to moderate AD 50 to 80 years of age were randomized 2:1 (crenezumab:placebo). Patients received low-dose subcutaneous crenezumab 300 mg or placebo every 2 weeks (n = 184) or high-dose intravenous crenezumab 15 mg/kg or placebo every 4 weeks (n = 247) for 68 weeks. Primary outcome measures were change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12) and Clinical Dementia Rating-Sum of Boxes scores from baseline to week 73...
April 25, 2018: Neurology
https://www.readbyqxmd.com/read/29695292/a-biomarker-study-in-long-lasting-amnestic-mild-cognitive-impairment
#17
Chiara Cerami, Alessandra Dodich, Sandro Iannaccone, Giuseppe Magnani, Roberto Santangelo, Luca Presotto, Alessandra Marcone, Luigi Gianolli, Stefano F Cappa, Daniela Perani
BACKGROUND: Mild cognitive impairment (MCI) is a heterogeneous syndrome resulting from Alzheimer's disease (AD) as well as to non-AD and non-neurodegenerative conditions. A subset of patients with amnestic MCI (aMCI) present with an unusually long-lasting course, a slow rate of clinical neuropsychological progression, and evidence of focal involvement of medial temporal lobe structures. In the present study, we explored positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers in a sample of subjects with aMCI with such clinical features in order to provide in vivo evidence to improve disease characterisation in this subgroup...
April 25, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29689726/differentiating-between-alzheimer-s-disease-and-vascular-cognitive-impairment-is-the-memory-versus-executive-function-contrast-still-relevant
#18
Daniela Andriuta, Martine Roussel, Mélanie Barbay, Sandrine Despretz-Wannepain, Olivier Godefroy
BACKGROUND: The contrast between memory versus executive function impairments is commonly used to differentiate between neurocognitive disorders (NCDs) due to Alzheimer's disease (AD) and vascular cognitive impairment (VCI). We reconsidered this question because of the current use of AD biomarkers and the recent revision of the criteria for AD, VCI, and dysexecutive syndrome. OBJECTIVE: To establish and compare the neuropsychological profiles in AD (i.e., with positive CSF biomarkers) and in VCI...
April 17, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29689725/a-systematic-review-and-aggregated-analysis-on-the-impact-of-amyloid-pet-brain-imaging-on-the-diagnosis-diagnostic-confidence-and-management-of-patients-being-evaluated-for-alzheimer-s-disease
#19
Enrico R Fantoni, Anastasia Chalkidou, John T O' Brien, Gill Farrar, Alexander Hammers
BACKGROUND: Amyloid PET (aPET) imaging could improve patient outcomes in clinical practice, but the extent of impact needs quantification. OBJECTIVE: To provide an aggregated quantitative analysis of the value added by aPET in cognitively impaired subjects. METHODS: Systematic literature searches were performed in Embase and Medline until January 2017. 1,531 cases over 12 studies were included (1,142 cases over seven studies in the primary analysis where aPET was the key biomarker; the remaining cases included as defined groups in the secondary analysis)...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29685286/soluble-trem2-and-biomarkers-of-central-and-peripheral-inflammation-in-neurodegenerative-disease
#20
L M Bekris, M Khrestian, E Dyne, Y Shao, J A Pillai, S M Rao, S M Bemiller, B Lamb, H H Fernandez, J B Leverenz
Alzheimer's disease (AD) has been genetically and pathologically associated with neuroinflammation. Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial receptor involved in innate immunity. TREM2 rare protein coding genetic variants have been linked to AD. A soluble TREM2 (sTREM2) cleavage product is elevated in AD. It is unclear whether there is a relationship between elevated sTREM2 and markers of inflammation. The hypothesis of this investigation was that central and peripheral inflammation play a role in sTREM2 levels in AD...
June 15, 2018: Journal of Neuroimmunology
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