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https://www.readbyqxmd.com/read/28644588/clinical-consensus-guidelines-on-the-application-of-cerebrospinal-fluid-biomarkers-for-alzheimer-s-disease-diagnosis-recommendations-of-the-irish-network-for-biomarkers-in-neurodegeneration
#1
A M Miller, E Begley, R Coen, M Doyle, J Dunne, S Hutchinson, S P Kennelly, R A Kenny, R P Killeen, A Lynch, S O'Dwyer, C O'Neill, S S O'Sullvan, M J Rowan, N Sheehy, C McGuigan, B A Lawlor
It is accepted that a lumbar puncture (LP) and cerebrospinal fluid (CSF) biomarker analysis support the routine diagnostic work-up for the differential diagnosis of dementia due to Alzheimer's disease (AD) within certain patient cohorts1. These tests, which measure CSF protein concentrations of amyloid-β42 (Aβ42), total tau (t-tau) and phospho tau (p-tau), were recently validated, accredited and made available clinically for the first time in Ireland. A working group, comprising Irish clinical and scientific researchers, met to review a) the validation results; b) international consensus opinions, and c) research and clinical evidence as to the clinical utility of CSF biomarker analysis for AD dementia diagnosis...
December 12, 2016: Irish Medical Journal
https://www.readbyqxmd.com/read/28641921/genome-wide-association-and-interaction-studies-of-csf-t-tau-a%C3%AE-42-ratio-in-adni-cohort
#2
Jin Li, Qiushi Zhang, Feng Chen, Xianglian Meng, Wenjie Liu, Dandan Chen, Jingwen Yan, Sungeun Kim, Lei Wang, Weixing Feng, Andrew J Saykin, Hong Liang, Li Shen
The pathogenic relevance in Alzheimer's disease (AD) presents a decrease of cerebrospinal fluid amyloid-ß42 (Aß42) burden and an increase in cerebrospinal fluid total tau (T-tau) levels. In this work, we performed genome-wide association study (GWAS) and genome-wide interaction study of T-tau/Aß42 ratio as an AD imaging quantitative trait on 843 subjects and 563,980 single-nucleotide polymorphisms (SNPs) in ADNI cohort. We aim to identify not only SNPs with significant main effects but also SNPs with interaction effects to help explain "missing heritability"...
May 15, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28638201/a-pilot-longitudinal-study-on-cerebrospinal-fluid-csf-tau-protein-in-alzheimer-s-disease-and-vascular-dementia
#3
Haihong Wang, Tao Wang, Shixing Qian, Li Ba, Zhiguang Lin, Shifu Xiao
BACKGROUND: Alzheimer's disease (AD) has high a prevalence rate, high medical costs, and care difficulties, and has become a serious social and economic problem in our aging society. So far, there has not been a reliable and objective diagnostic criteria for AD found. In recent years, there have been many domestic and foreign studies on the biological markers of cerebrospinal fluid in the patients with AD, and high levels of the T-tau, P-tau found in cerebrospinal fluid (CSF) is at this point an indisputable fact...
October 25, 2016: Shanghai Archives of Psychiatry
https://www.readbyqxmd.com/read/28628634/protein-signature-in-cerebrospinal-fluid-and-serum-of-alzheimer-s-disease-patients-the-case-of-apolipoprotein-a-1-proteoforms
#4
Chiara Fania, Beatrice Arosio, Daniele Capitanio, Enrica Torretta, Cristina Gussago, Evelyn Ferri, Daniela Mari, Cecilia Gelfi
In the diagnosis of Alzheimer's disease (AD) total tau (T-tau), tau phosphorylated at threonine 181 (P-tau181), and the 42 amino acid isoform of alpha β-amyloid (Aβ) are well established surrogate CSF markers. However, there is a constant need for new diagnostic markers to identify the disease at a very early stage. The identification of new molecules for AD diagnosis and monitoring in CSF is hampered by several "confounding" factors including intra- and inter-individual, pre-analytical and analytical variabilities...
2017: PloS One
https://www.readbyqxmd.com/read/28623948/one-carbon-metabolism-cognitive-impairment-and-csf-measures-of-alzheimer-pathology-homocysteine-and-beyond
#5
Loïc Dayon, Seu Ping Guiraud, John Corthésy, Laeticia Da Silva, Eugenia Migliavacca, Domilė Tautvydaitė, Aikaterini Oikonomidi, Barbara Moullet, Hugues Henry, Sylviane Métairon, Julien Marquis, Patrick Descombes, Sebastiano Collino, François-Pierre J Martin, Ivan Montoliu, Martin Kussmann, Jérôme Wojcik, Gene L Bowman, Julius Popp
BACKGROUND: Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults...
June 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28618005/bace1-inhibitor-lanabecestat-azd3293-in-a-phase-1-study-of-healthy-japanese-subjects-pharmacokinetics-and-effects-on-plasma-and-cerebrospinal-fluid-a%C3%AE-peptides
#6
Kei Sakamoto, Shunji Matsuki, Kyoko Matsuguma, Tatsuya Yoshihara, Naoki Uchida, Fumihiko Azuma, Muir Russell, Glen Hughes, Samantha Budd Haeberlein, Robert C Alexander, Susanna Eketjäll, Alan R Kugler
Lanabecestat (AZD3293; LY3314814) is an orally active potent inhibitor of human β-secretase 1 in clinical development for the treatment of Alzheimer disease. In this first Japanese clinical study for an Alzheimer disease intervention to include cerebrospinal fluid (CSF) sampling in Japanese elderly healthy subjects, we report the pharmacokinetics and effects on plasma and CSF amyloid-β (Aβ) peptides of lanabecestat in a phase 1 study involving 40 healthy Japanese subjects (NCT02005211). No safety and tolerability concerns were identified in healthy Japanese subjects exposed to lanabecestat up to the highest doses given, which is consistent with observations in a US phase 1 study of lanabecestat...
June 15, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28604243/the-use-of-cerebrospinal-fluid-biomarkers-to-measure-change-in-neurodegeneration-in-alzheimer-s-disease-clinical-trials
#7
Bob Olsson, Jonathan M Schott, Kaj Blennow, Henrik Zetterberg
All recent phase 3 trials of potentially disease-modifying therapies for Alzheimer's disease (AD) have so far failed. Potential reasons include enrolling subjects whose disease is too advanced or who do not have AD pathology, or simply incorrect drug targets. The goal of disease-modifying AD trials is to halt the progress of neuronal damage and death and this can be assessed in vivo using cerebrospinal fluid (CSF) biomarkers. Areas covered: The authors conducted a literature search of the use of CSF biomarkers in disease-modifying AD clinical trials using PubMed...
June 19, 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/28600739/association-of-longitudinal-white-matter-degeneration-and-cerebrospinal-fluid-biomarkers-of-neurodegeneration-inflammation-and-alzheimer-s-disease-in-late-middle-aged-adults
#8
Annie M Racine, Andrew P Merluzzi, Nagesh Adluru, Derek Norton, Rebecca L Koscik, Lindsay R Clark, Sara E Berman, Christopher R Nicholas, Sanjay Asthana, Andrew L Alexander, Kaj Blennow, Henrik Zetterberg, Won Hwa Kim, Vikas Singh, Cynthia M Carlsson, Barbara B Bendlin, Sterling C Johnson
Alzheimer's disease (AD) is characterized by substantial neurodegeneration, including both cortical atrophy and loss of underlying white matter fiber tracts. Understanding longitudinal alterations to white matter may provide new insights into trajectories of brain change in both healthy aging and AD, and fluid biomarkers may be particularly useful in this effort. To examine this, 151 late-middle-aged participants enriched with risk for AD with at least one lumbar puncture and two diffusion tensor imaging (DTI) scans were selected for analysis from two large observational and longitudinally followed cohorts...
June 9, 2017: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/28598844/combustion-derived-nanoparticles-in-key-brain-target-cells-and-organelles-in-young-urbanites-culprit-hidden-in-plain-sight-in-alzheimer-s-disease-development
#9
Angélica González-Maciel, Rafael Reynoso-Robles, Ricardo Torres-Jardón, Partha S Mukherjee, Lilian Calderón-Garcidueñas
Millions of children and young adults are exposed to fine particulate matter (PM2.5) and ozone, associated with Alzheimer's disease (AD) risk. Mexico City (MC) children exhibit systemic and brain inflammation, low cerebrospinal fluid (CSF) Aβ1-42, breakdown of nasal, olfactory, alveolar-capillary, duodenal, and blood-brain barriers, volumetric and metabolic brain changes, attention and short-term memory deficits, and hallmarks of AD and Parkinson's disease. Airborne iron-rich strongly magnetic combustion-derived nanoparticles (CDNPs) are present in young urbanites' brains...
June 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28595794/a-systematic-review-and-meta-analysis-of-the-circulatory-erythrocellular-and-csf-selenium-levels-in-alzheimer-s-disease-a-metal-meta-analysis-amma-study-i
#10
Varikasuvu Seshadri Reddy, Suman Bukke, Naveen Dutt, Puneet Rana, Arun Kumar Pandey
BACKGROUND: Available studies in the literature on the selenium levels in Alzheimer's disease (AD) are inconsistent with some studies reporting its decrease in the circulation, while others reported an increase or no change as compared to controls. AIM: The objective of this study was to perform a meta-analysis of circulatory (plasma/serum and blood), erythrocyte and cerebrospinal fluid (CSF) selenium levels in AD compared controls. We also performed a meta-analysis of the correlation coefficients (r) to demonstrate the associations between selenium and glutathione peroxidase (GPx) in AD patients...
July 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/28592456/csf-sapp%C3%AE-ykl-40-and-neurofilament-light-in-frontotemporal-lobar-degeneration
#11
Daniel Alcolea, Eduard Vilaplana, Marc Suárez-Calvet, Ignacio Illán-Gala, Rafael Blesa, Jordi Clarimón, Albert Lladó, Raquel Sánchez-Valle, José L Molinuevo, Guillermo García-Ribas, Yaroslau Compta, María José Martí, Gerard Piñol-Ripoll, Guillermo Amer-Ferrer, Aina Noguera, Ana García-Martín, Juan Fortea, Alberto Lleó
OBJECTIVE: To analyze the clinical utility of 3 CSF biomarkers and their structural imaging correlates in a large cohort of patients with different dementia and parkinsonian syndromes within the spectrum of frontotemporal lobar degeneration (FTLD). METHODS: We analyzed 3 CSF biomarkers (YKL-40, soluble β fragment of amyloid precursor protein [sAPPβ], neurofilament light [NfL]) and core Alzheimer disease (AD) biomarkers (β-amyloid1-42, total tau, phosphorylated tau) in patients with FTLD-related clinical syndromes (n = 159): behavioral variant of frontotemporal dementia (n = 68), nonfluent (n = 23) and semantic (n = 19) variants of primary progressive aphasia, progressive supranuclear palsy (n = 28), and corticobasal syndrome (n = 21)...
June 7, 2017: Neurology
https://www.readbyqxmd.com/read/28592211/calmodulin-like-skin-protein-is-downregulated-in-human-cerebrospinal-fluids-of-alzheimer-s-disease-patients-with-apolipoprotein-e4-a-pilot-study-using-postmortem-samples
#12
Yuichi Hashimoto, Takahiko Umahara, Haruo Hanyu, Toshihiko Iwamoto, Masaaki Matsuoka
OBJECTIVE: Calmodulin-like skin protein (CLSP) is a secreted peptide that inhibits neuronal cell death, linked to Alzheimer's disease (AD), by binding to the heterotrimeric humanin receptor and activating an intracellular survival pathway. CLSP is only expressed in skin keratinocytes and related epithelial cells, circulates in the blood stream, and passes the blood-cerebrospinal fluid (CSF) barrier. In the current study, we addressed the issues as to whether CLSP functions in the central nervous system and whether the concentration of CLSP is reduced in the CSFs of AD patients...
June 7, 2017: Neurological Research
https://www.readbyqxmd.com/read/28589856/association-analysis-of-rare-variants-near-the-apoe-region-with-csf-and-neuroimaging-biomarkers-of-alzheimer-s-disease
#13
Kwangsik Nho, Sungeun Kim, Emrin Horgusluoglu, Shannon L Risacher, Li Shen, Dokyoon Kim, Seunggeun Lee, Tatiana Foroud, Leslie M Shaw, John Q Trojanowski, Paul S Aisen, Ronald C Petersen, Clifford R Jack, Michael W Weiner, Robert C Green, Arthur W Toga, Andrew J Saykin
BACKGROUND: The APOE ε4 allele is the most significant common genetic risk factor for late-onset Alzheimer's disease (LOAD). The region surrounding APOE on chromosome 19 has also shown consistent association with LOAD. However, no common variants in the region remain significant after adjusting for APOE genotype. We report a rare variant association analysis of genes in the vicinity of APOE with cerebrospinal fluid (CSF) and neuroimaging biomarkers of LOAD. METHODS: Whole genome sequencing (WGS) was performed on 817 blood DNA samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI)...
May 24, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28587660/recommendations-for-cerebrospinal-fluid-collection-for-the-analysis-by-elisa-of-neurogranin-trunc-p75-%C3%AE-synuclein-and-total-tau-in-combination-with-a%C3%AE-1-42-a%C3%AE-1-40
#14
Hugo Vanderstichele, Leentje Demeyer, Shorena Janelidze, Els Coart, Erik Stoops, Kimberley Mauroo, Victor Herbst, Cindy François, Oskar Hansson
BACKGROUND: The pathophysiology of neurodegeneration is complex. Its diagnosis requires an early identification of sequential changes in several hallmarks in the brains of affected subjects. The presence of brain pathology can be visualized in the cerebrospinal fluid (CSF) by protein profiling. It is clear that the field of Alzheimer's disease (AD) will benefit from an integration of algorithms including CSF concentrations of individual proteins, especially as an aid in clinical decision-making or to improve patient enrolment in clinical trials...
June 6, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28587659/glutaminyl-cyclase-activity-correlates-with-levels-of-a%C3%AE-peptides-and-mediators-of-angiogenesis-in-cerebrospinal-fluid-of-alzheimer-s-disease-patients
#15
Claire Bridel, Torsten Hoffmann, Antje Meyer, Sisi Durieux, Marleen A Koel-Simmelink, Matthias Orth, Philip Scheltens, Inge Lues, Charlotte E Teunissen
BACKGROUND: Pyroglutamylation of truncated Aβ peptides, which is catalysed by enzyme glutaminyl cyclase (QC), generates pE-Aβ species with enhanced aggregation propensities and resistance to most amino-peptidases and endo-peptidases. pE-Aβ species have been identified as major constituents of Aβ plaques and reduction of pE-Aβ species is associated with improvement of cognitive tasks in animal models of Alzheimer's disease (AD). Pharmacological inhibition of QC has thus emerged as a promising therapeutic approach for AD...
June 6, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28585290/csf-biomarkers-in-delirium-a-systematic-review
#16
Roanna J Hall, Leiv Otto Watne, Emma Cunningham, Henrik Zetterberg, Susan D Shenkin, Torgeir Bruun Wyller, Alasdair M J MacLullich
OBJECTIVE: In recent years, there has been a blossoming of studies examining cerebrospinal fluid (CSF) as a method of studying the pathophysiology of delirium. We systematically reviewed the literature for CSF studies in delirium and provide here a summary of the implications for our understanding of delirium pathophysiology. We also summarise the methods used for CSF analysis and discuss challenges and implications for future studies. METHODS: In this systematic review, we screened MEDLINE, EMBASE, PsycINFO, Web of Science, PubMed and the Cochrane Library for articles on CSF biomarkers in delirium, published on 3 September 2016...
June 6, 2017: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28579942/voluntary-exercise-promotes-glymphatic-clearance-of-amyloid-beta-and-reduces-the-activation-of-astrocytes-and-microglia-in-aged-mice
#17
Xiao-Fei He, Dong-Xu Liu, Qun Zhang, Feng-Ying Liang, Guang-Yan Dai, Jin-Sheng Zeng, Zhong Pei, Guang-Qing Xu, Yue Lan
Age is characterized by chronic inflammation, leading to synaptic dysfunction and dementia because the clearance of protein waste is reduced. The clearance of proteins depends partly on the permeation of the blood-brain barrier (BBB) or on the exchange of water and soluble contents between the cerebrospinal fluid (CSF) and the interstitial fluid (ISF). A wealth of evidence indicates that physical exercise improves memory and cognition in neurodegenerative diseases during aging, such as Alzheimer's disease (AD), but the influence of physical training on glymphatic clearance, BBB permeability and neuroinflammation remains unclear...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28578726/statistically-derived-subtypes-and-associations-with-cerebrospinal-fluid-and-genetic-biomarkers-in-mild-cognitive-impairment-a-latent-profile-analysis
#18
Joel S Eppig, Emily C Edmonds, Laura Campbell, Mark Sanderson-Cimino, Lisa Delano-Wood, Mark W Bondi
OBJECTIVES: Research demonstrates heterogeneous neuropsychological profiles among individuals with mild cognitive impairment (MCI). However, few studies have included visuoconstructional ability or used latent mixture modeling to statistically identify MCI subtypes. Therefore, we examined whether unique neuropsychological MCI profiles could be ascertained using latent profile analysis (LPA), and subsequently investigated cerebrospinal fluid (CSF) biomarkers, genotype, and longitudinal clinical outcomes between the empirically derived classes...
June 5, 2017: Journal of the International Neuropsychological Society: JINS
https://www.readbyqxmd.com/read/28574812/associations-between-apoe-genotype-and-cerebral-small-vessel-disease-a-longitudinal-study
#19
Xiao Luo, Yerfan Jiaerken, Xinfeng Yu, Peiyu Huang, Tiantian Qiu, Yunlu Jia, Kaicheng Li, Xiaojun Xu, Zhujing Shen, Xiaojun Guan, Jiong Zhou, Minming Zhang
OBJECTIVE: It remains unclear if and how the interactions between APOE genotypes and cerebral small-vessel diseases (CSVD) lead to cognitive decline in the long term. Based on ADNI cohort, this longitudinal study aimed to clarify the potential relationship among APOE genotype, CSVD and cognition by integrating multi-level data. METHOD: There were 135 healthy elderly (including ε2, ε4 allele carriers and ε3 homozygotes) who had completed two years' follow-up. MRI markers of CSVD, including white matter hyperintensities (WMH), dilated perivascular space (dPVS), microbleeds and lacune, were assessed...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28571653/csf-apoe-predicts-clinical-progression-in-nondemented-apoe%C3%AE%C2%B54-carriers
#20
Argonde C van Harten, Wesley Jongbloed, Charlotte E Teunissen, Philip Scheltens, Rob Veerhuis, Wiesje M van der Flier
Possible associations between cerebrospinal fluid (CSF) and plasma apolipoprotein E (ApoE) concentration and early clinical and pathophysiological manifestation of Alzheimer's disease were studied in a large and well-defined population of nondemented patients. CSF and plasma ApoE concentrations were related to CSF Aβ42, Tau and pTau levels and clinical characteristics in patients with subjective cognitive decline (n = 207) or mild cognitive impairment (n = 213) aged 64.2 ± 9.0 years, with a 2.5 ± 1.5 years follow-up...
April 12, 2017: Neurobiology of Aging
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