Increased Neurofilament Light Chain Blood Levels in Neurodegenerative Neurological Diseases
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{"title"=>"Increased Neurofilament Light Chain Blood Levels in Neurodegenerative Neurological Diseases", "type"=>"journal", "authors"=>[{"first_name"=>"Johanna", "last_name"=>"Gaiottino", "scopus_author_id"=>"24278783500"}, {"first_name"=>"Niklas", "last_name"=>"Norgren", "scopus_author_id"=>"6507640983"}, {"first_name"=>"Ruth", "last_name"=>"Dobson", "scopus_author_id"=>"36093903900"}, {"first_name"=>"Joanne", "last_name"=>"Topping", "scopus_author_id"=>"55347725200"}, {"first_name"=>"Ahuva", "last_name"=>"Nissim", "scopus_author_id"=>"6701724009"}, {"first_name"=>"Andrea", "last_name"=>"Malaspina", "scopus_author_id"=>"7003290890"}, {"first_name"=>"Jonathan P.", "last_name"=>"Bestwick", "scopus_author_id"=>"14027999700"}, {"first_name"=>"Andreas U.", "last_name"=>"Monsch", "scopus_author_id"=>"7003427149"}, {"first_name"=>"Axel", "last_name"=>"Regeniter", "scopus_author_id"=>"6602956656"}, {"first_name"=>"Raija L.", "last_name"=>"Lindberg", "scopus_author_id"=>"7101777836"}, {"first_name"=>"Ludwig", "last_name"=>"Kappos", "scopus_author_id"=>"7004559324"}, {"first_name"=>"David", "last_name"=>"Leppert", "scopus_author_id"=>"7003711670"}, {"first_name"=>"Axel", "last_name"=>"Petzold", "scopus_author_id"=>"7006826396"}, {"first_name"=>"Gavin", "last_name"=>"Giovannoni", "scopus_author_id"=>"34770127900"}, {"first_name"=>"Jens", "last_name"=>"Kuhle", "scopus_author_id"=>"8937520800"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84884497586", "doi"=>"10.1371/journal.pone.0075091", "pui"=>"369867996", "pmid"=>"24073237", "scopus"=>"2-s2.0-84884497586", "issn"=>"19326203", "isbn"=>"1932-6203"}, "id"=>"97ebccea-7af2-3baa-8297-0f22afc4ea9c", "abstract"=>"OBJECTIVE Neuronal damage is the morphological substrate of persisting neurological disability. Neurofilaments (Nf) are cytoskeletal proteins of neurons and their release into cerebrospinal fluid has shown encouraging results as a biomarker for neurodegeneration. This study aimed to validate the quantification of the Nf light chain (NfL) in blood samples, as a biofluid source easily accessible for longitudinal studies. METHODS We developed and applied a highly sensitive electrochemiluminescence (ECL) based immunoassay for quantification of NfL in blood and CSF. RESULTS Patients with Alzheimer's disease (AD) (30.8 pg/ml, n=20), Guillain-Barré-syndrome (GBS) (79.4 pg/ml, n=19) or amyotrophic lateral sclerosis (ALS) (95.4 pg/ml, n=46) had higher serum NfL values than a control group of neurological patients without evidence of structural CNS damage (control patients, CP) (4.4 pg/ml, n=68, p<0.0001 for each comparison, p=0.002 for AD patients) and healthy controls (HC) (3.3 pg/ml, n=67, p<0.0001). Similar differences were seen in corresponding CSF samples. CSF and serum levels correlated in AD (r=0.48, p=0.033), GBS (r=0.79, p<0.0001) and ALS (r=0.70, p<0.0001), but not in CP (r=0.11, p=0.3739). The sensitivity and specificity of serum NfL for separating ALS from healthy controls was 91.3% and 91.0%. CONCLUSIONS We developed and validated a novel ECL based sandwich immunoassay for the NfL protein in serum (NfL(Umea47:3)); levels in ALS were more than 20-fold higher than in controls. Our data supports further longitudinal studies of serum NfL in neurodegenerative diseases as a potential biomarker of on-going disease progression, and as a potential surrogate to quantify effects of neuroprotective drugs in clinical trials.", "link"=>"http://www.mendeley.com/research/increased-neurofilament-light-chain-blood-levels-neurodegenerative-neurological-diseases", "reader_count"=>120, "reader_count_by_academic_status"=>{"Unspecified"=>6, "Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>28, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>28, "Student > Postgraduate"=>6, "Student > Master"=>14, "Other"=>8, "Student > Bachelor"=>16, "Lecturer > Senior Lecturer"=>1, "Professor"=>7}, "reader_count_by_user_role"=>{"Unspecified"=>6, "Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>28, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>28, "Student > Postgraduate"=>6, "Student > Master"=>14, "Other"=>8, "Student > Bachelor"=>16, "Lecturer > Senior Lecturer"=>1, "Professor"=>7}, "reader_count_by_subject_area"=>{"Unspecified"=>12, "Nursing and Health Professions"=>2, "Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>29, "Medicine and Dentistry"=>49, "Neuroscience"=>17, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Veterinary Science and Veterinary Medicine"=>1, "Chemistry"=>1, "Psychology"=>1, "Decision Sciences"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>49}, "Neuroscience"=>{"Neuroscience"=>17}, "Chemistry"=>{"Chemistry"=>1}, "Decision Sciences"=>{"Decision Sciences"=>1}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>29}, "Computer Science"=>{"Computer Science"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>12}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Austria"=>1, "Netherlands"=>1, "United States"=>1, "Brazil"=>1, "United Kingdom"=>2}, "group_count"=>7}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1211642"], "description"=>"<p>Patients with Amyotrophic lateral sclerosis (ALS) (5513 pg/ml) or a Guillain-Barré syndrome (GBS) (1361 pg/ml) had higher levels than CP (324 pg/ml, p<0.0001 and p=0.001). In addition ALS had higher levels than patients with Alzheimer’s disease (AD) (1361 pg/ml) and GBS (p<0.0001, respectively). Geometric mean and 95% CI are displayed. Dots represent individual samples. P-values are adjusted for age and corrected by Bonferroni method.</p>", "links"=>[], "tags"=>["nfl", "neurological"], "article_id"=>804909, "categories"=>["Biological Sciences"], "users"=>["Johanna Gaiottino", "Niklas Norgren", "Ruth Dobson", "Joanne Topping", "Ahuva Nissim", "Andrea Malaspina", "Jonathan P. Bestwick", "Andreas U. Monsch", "Axel Regeniter", "Raija L. Lindberg", "Ludwig Kappos", "David Leppert", "Axel Petzold", "Gavin Giovannoni", "Jens Kuhle"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0075091.g004", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CSF_NfL_levels_in_the_reference_group_control_patients_CP_and_neurological_disease_cohorts_/804909", "title"=>"CSF NfL levels in the reference group (control patients, CP) and neurological disease cohorts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-20 02:17:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/1211643"], "description"=>"<p>Serum and CSF measurements of NfL correlated in the disease groups (A): Alzheimer’s disease (AD) (r=0.48, p=0.033), Guillain-Barré syndrome (GBS) (r=0.79, p<0.0001) and Amyotrophic lateral sclerosis (ALS) (r=0.70, p<0.0001): overall: r=0.68, p<0.001. Conversely this was not seen in the control patients (CP) (r=0.11, p=0.3739) (B).</p>", "links"=>[], "tags"=>["serum", "csf", "nfl"], "article_id"=>804910, "categories"=>["Biological Sciences"], "users"=>["Johanna Gaiottino", "Niklas Norgren", "Ruth Dobson", "Joanne Topping", "Ahuva Nissim", "Andrea Malaspina", "Jonathan P. Bestwick", "Andreas U. Monsch", "Axel Regeniter", "Raija L. Lindberg", "Ludwig Kappos", "David Leppert", "Axel Petzold", "Gavin Giovannoni", "Jens Kuhle"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0075091.g005", "stats"=>{"downloads"=>1, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Correlation_of_serum_and_CSF_NfL_measurements_/804910", "title"=>"Correlation of serum and CSF NfL measurements.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-20 02:17:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/1211640"], "description"=>"<p>Parallelism for NfL between standards (open line, open dots) and serum (closed line, black squares). The linear regression lines, mean (open dots or black squares) and ±SD are shown.</p>", "links"=>[], "tags"=>["standards", "serum"], "article_id"=>804907, "categories"=>["Biological Sciences"], "users"=>["Johanna Gaiottino", "Niklas Norgren", "Ruth Dobson", "Joanne Topping", "Ahuva Nissim", "Andrea Malaspina", "Jonathan P. Bestwick", "Andreas U. Monsch", "Axel Regeniter", "Raija L. Lindberg", "Ludwig Kappos", "David Leppert", "Axel Petzold", "Gavin Giovannoni", "Jens Kuhle"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0075091.g002", "stats"=>{"downloads"=>0, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Parallelism_between_standards_and_serum_dilutions_/804907", "title"=>"Parallelism between standards and serum dilutions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-20 02:17:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/1211641"], "description"=>"<p>Patients with a Guillain-Barré syndrome (GBS) (79.4 pg/ml) or Amyotrophic lateral sclerosis (ALS) (95.4 pg/ml) had higher values compared with HC (3.3 pg/ml; p<0.0001, respectively) and CP (4.4 pg/ml, p<0.0001 and p=0.001). Significances for comparisons between patients with Alzheimer’s disease (AD) and HC (p<0.0001) and AD and CP (p=0.002) were lost after age corrections. The horizontal dotted line represents the upper reference range (cut-off value) of 26.6 pg/ml. Geometric mean and 95% CI are displayed. Dots represent individual samples. P-values are adjusted for age and corrected by Bonferroni method.</p>", "links"=>[], "tags"=>["nfl", "groups", "hc", "neurological"], "article_id"=>804908, "categories"=>["Biological Sciences"], "users"=>["Johanna Gaiottino", "Niklas Norgren", "Ruth Dobson", "Joanne Topping", "Ahuva Nissim", "Andrea Malaspina", "Jonathan P. Bestwick", "Andreas U. Monsch", "Axel Regeniter", "Raija L. Lindberg", "Ludwig Kappos", "David Leppert", "Axel Petzold", "Gavin Giovannoni", "Jens Kuhle"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0075091.g003", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Serum_NfL_levels_in_the_two_reference_groups_healthy_controls_HC_and_control_patients_CP_and_neurological_disease_groups_/804908", "title"=>"Serum NfL levels in the two reference groups (healthy controls, HC and control patients, CP) and neurological disease groups.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-20 02:17:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/1211639"], "description"=>"<p>Reproducibility of 20 consecutive standard curves. The graph shows the mean counts (dots) ± SD (bars), linear regression line and 5% and 95% confidence interval curves (broken lines) (R<sup>2</sup>=0.99).</p>", "links"=>[], "tags"=>[], "article_id"=>804906, "categories"=>["Biological Sciences"], "users"=>["Johanna Gaiottino", "Niklas Norgren", "Ruth Dobson", "Joanne Topping", "Ahuva Nissim", "Andrea Malaspina", "Jonathan P. Bestwick", "Andreas U. Monsch", "Axel Regeniter", "Raija L. Lindberg", "Ludwig Kappos", "David Leppert", "Axel Petzold", "Gavin Giovannoni", "Jens Kuhle"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0075091.g001", "stats"=>{"downloads"=>2, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reproducibility_of_the_standard_curve_/804906", "title"=>"Reproducibility of the standard curve.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-20 02:17:19"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"43", "full-text"=>"46", "pdf"=>"15", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"19", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"66", "full-text"=>"73", "pdf"=>"24", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}

Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[266, 468, 593, 703, 804, 903, 993, 1084, 1171, 1256, 1339, 1422, 1492]}, {"subject_area"=>"/Medicine and health sciences/Diagnostic medicine", "average_usage"=>[244, 425, 535, 636, 728, 814, 900, 982, 1063, 1139, 1221, 1296, 1361]}, {"subject_area"=>"/Medicine and health sciences/Hematology", "average_usage"=>[238, 424, 545, 650, 749, 839, 926, 1006, 1090, 1167, 1243, 1316, 1380]}, {"subject_area"=>"/Medicine and health sciences/Neurology", "average_usage"=>[271, 485, 617, 733, 835, 933, 1026, 1115, 1207, 1294, 1386, 1475, 1543]}, {"subject_area"=>"/Medicine and health sciences/Physiology", "average_usage"=>[258, 449, 572, 679, 775, 866, 956, 1041, 1124, 1211, 1291, 1371, 1437]}]}
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