{"doi":"10.1159/000444788","title":"Cerebrospinal Fluid TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis Patients with and without the C9ORF72 Hexanucleotide Expansion","abstract":"<b><i>Background:</i></b> TDP-43 is the main protein component of ubiquitinated inclusions in a subgroup of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) patients. The <i>C9ORF72</i> hexanucleotide expansion is one of the main mutations associated with TDP-43 pathology in FTLD and ALS. Our aim was to analyze cerebrospinal fluid (CSF) TDP-43 levels and Alzheimer's disease biomarkers in FTLD and ALS patients and to test whether the <i>C9ORF72</i> expansion carrier status affects these variables. <b><i>Methods:</i></b> The patient cohort consisted of 90 clinically well-characterized FTLD (n = 69) and ALS (n = 21) patients. There were 30 patients with the <i>C9ORF72</i> expansion and 60 patients without the expansion. CSF TDP-43, Aβ<sub>1-42</sub>, t-tau, and phospho-tau levels were measured using commercial ELISA kits. <b><i>Results:</i></b> There was no difference in CSF TDP-43 levels between the <i>C9ORF72</i> expansion carriers and the noncarriers. CSF TDP-43 levels were higher in ALS patients than in FTLD patients, and this finding was independent of the <i>C9ORF72</i> expansion carrier status. Males had significantly higher TDP-43 levels than females (p = 0.008 in the total cohort). <b><i>Conclusion:</i></b> CSF TDP-43 does not seem to distinguish the <i>C9ORF72</i> expansion carriers from noncarriers. However, higher CSF TDP-43 levels were detected in ALS than in FTLD, which might be an indicator of a more rapid progression of TDP-43 pathology in ALS.","journal":"Dementia and Geriatric Cognitive Disorders Extra","year":2016,"id":594596,"datarank":0.5955437870328184,"base_score":3.970291913552122,"endowment":3.970291913552122,"self_citation_contribution":0.5955437870328184,"citation_network_contribution":0.0,"self_endowment_contribution":0.5955437870328184,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":52,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1522187,"name":"Mari Kuvaja","orcid":null,"position":1,"is_corresponding":false},{"id":1522188,"name":"Päivi Hartikainen","orcid":null,"position":2,"is_corresponding":false},{"id":1522189,"name":"Maritta Siloaho","orcid":null,"position":3,"is_corresponding":false},{"id":846030,"name":"Seppo Helisalmi","orcid":"0000-0003-3982-2397","position":4,"is_corresponding":false},{"id":1522190,"name":"Virpi Moilanen","orcid":null,"position":5,"is_corresponding":false},{"id":1522191,"name":"Anna Kiviharju","orcid":null,"position":6,"is_corresponding":false},{"id":899242,"name":"Lilja Jansson","orcid":null,"position":7,"is_corresponding":false},{"id":95138,"name":"Pentti J. Tienari","orcid":"0000-0001-5686-2900","position":8,"is_corresponding":false},{"id":1522192,"name":"Anne Marja Remes","orcid":null,"position":9,"is_corresponding":false},{"id":1362314,"name":"Sanna-Kaisa Herukka","orcid":null,"position":10,"is_corresponding":false},{"id":1522186,"name":"Anna Junttila","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Cerebrospinal Fluid TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis Patients with and without the C9ORF72 Hexanucleotide Expansion","abstract":"<b><i>Background:</i></b> TDP-43 is the main protein component of ubiquitinated inclusions in a subgroup of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) patients. The <i>C9ORF72</i> hexanucleotide expansion is one of the main mutations associated with TDP-43 pathology in FTLD and ALS. Our aim was to analyze cerebrospinal fluid (CSF) TDP-43 levels and Alzheimer's disease biomarkers in FTLD and ALS patients and to test whether the <i>C9ORF72</i> expansion carrier status affects these variables. <b><i>Methods:</i></b> The patient cohort consisted of 90 clinically well-characterized FTLD (n = 69) and ALS (n = 21) patients. There were 30 patients with the <i>C9ORF72</i> expansion and 60 patients without the expansion. CSF TDP-43, Aβ<sub>1-42</sub>, t-tau, and phospho-tau levels were measured using commercial ELISA kits. <b><i>Results:</i></b> There was no difference in CSF TDP-43 levels between the <i>C9ORF72</i> expansion carriers and the noncarriers. CSF TDP-43 levels were higher in ALS patients than in FTLD patients, and this finding was independent of the <i>C9ORF72</i> expansion carrier status. Males had significantly higher TDP-43 levels than females (p = 0.008 in the total cohort). <b><i>Conclusion:</i></b> CSF TDP-43 does not seem to distinguish the <i>C9ORF72</i> expansion carriers from noncarriers. However, higher CSF TDP-43 levels were detected in ALS than in FTLD, which might be an indicator of a more rapid progression of TDP-43 pathology in ALS.","is_dataset_classified":null,"base_score":3.970291913552122,"endowment":3.970291913552122,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"27195002","pmcid":"PMC4868946","openalex_id":"https://openalex.org/W2336205378","authors":[],"funders":[{"funder_name":"Research Council of Finland","grant_id":"263193","title":"Biomarkers for Alzheimer’s disease and Parkinson’s disease"}],"total_grants":1,"fwci":3.7961,"citation_percentile":0.9321903,"influential_citations":3,"citation_trend":[{"year":2016,"count":1},{"year":2017,"count":4},{"year":2018,"count":8},{"year":2019,"count":5},{"year":2020,"count":4},{"year":2021,"count":8},{"year":2022,"count":6},{"year":2023,"count":5},{"year":2024,"count":4},{"year":2025,"count":4},{"year":2026,"count":3}],"oa_status":"gold","license":"cc-by-nc-nd","oa_locations":[{"url":"https://www.karger.com/Article/Pdf/444788","host_type":"journal"},{"url":"https://www.karger.com/Article/Pdf/444788","host_type":"GOLD"},{"url":"https://www.karger.com/Article/Pdf/444788","host_type":"publisher"},{"url":"https://doi.org/10.1159/000444788","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/27195002","host_type":"repository"},{"url":"https://doaj.org/article/fb5a4805381d49f09c4612bfc66e63ba","host_type":"repository"},{"url":"https://erepo.uef.fi/handle/123456789/158","host_type":"repository"},{"url":"http://hdl.handle.net/10138/175069","host_type":"journal"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4868946","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC4868946","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC4868946?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1159/000444788","host_type":""},{"url":"https://dx.doi.org/10.1159/000444788","host_type":""},{"url":"http://doi.org/10.1159/000444788","host_type":""},{"url":"https://doi.org/https://doi.org/10.1159/000444788","host_type":""}],"fields_of_study":["Amyotrophic Lateral Sclerosis Research","Genetic Neurodegenerative Diseases","Cerebrospinal fluid and hydrocephalus","Medicine","03 medical and health sciences","0302 clinical medicine"],"mesh_terms":[],"keywords":["C9orf72","Frontotemporal lobar degeneration","Amyotrophic lateral sclerosis","Frontotemporal dementia","Cerebrospinal fluid","Pathology","Medicine","Cohort","Motor neurone disease","Internal medicine","Dementia","Oncology","Psychology","Disease","ELISA","Biomarker","Tdp-43","RC952-954.6","Geriatrics","Neurology. Diseases of the nervous system","Original Research Article","RC346-429"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T14:59:32.785140Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}