Cerebrospinal Fluid TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis Patients with and without the C9ORF72 Hexanucleotide Expansion
Background: 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 C9ORF72 hexanucleotide expansion is one of the main mutations associated with TDP-43 pathology in FTLD and ALS....
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Karger Publishers
2016-04-01
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| Series: | Dementia and Geriatric Cognitive Disorders Extra |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/444788 |
| _version_ | 1818520761290194944 |
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| author | Anna Junttila Mari Kuvaja Päivi Hartikainen Maritta Siloaho Seppo Helisalmi Virpi Moilanen Anna Kiviharju Lilja Jansson Pentti J. Tienari Anne Marja Remes Sanna-Kaisa Herukka |
| author_facet | Anna Junttila Mari Kuvaja Päivi Hartikainen Maritta Siloaho Seppo Helisalmi Virpi Moilanen Anna Kiviharju Lilja Jansson Pentti J. Tienari Anne Marja Remes Sanna-Kaisa Herukka |
| author_sort | Anna Junttila |
| collection | DOAJ |
| description | Background: 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 C9ORF72 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 C9ORF72 expansion carrier status affects these variables. Methods: The patient cohort consisted of 90 clinically well-characterized FTLD (n = 69) and ALS (n = 21) patients. There were 30 patients with the C9ORF72 expansion and 60 patients without the expansion. CSF TDP-43, Aβ1-42, t-tau, and phospho-tau levels were measured using commercial ELISA kits. Results: There was no difference in CSF TDP-43 levels between the C9ORF72 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 C9ORF72 expansion carrier status. Males had significantly higher TDP-43 levels than females (p = 0.008 in the total cohort). Conclusion: CSF TDP-43 does not seem to distinguish the C9ORF72 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. |
| first_indexed | 2024-12-11T01:42:00Z |
| format | Article |
| id | doaj.art-fb5a4805381d49f09c4612bfc66e63ba |
| institution | Directory Open Access Journal |
| issn | 1664-5464 |
| language | English |
| last_indexed | 2024-12-11T01:42:00Z |
| publishDate | 2016-04-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Dementia and Geriatric Cognitive Disorders Extra |
| spelling | doaj.art-fb5a4805381d49f09c4612bfc66e63ba2022-12-22T01:25:02ZengKarger PublishersDementia and Geriatric Cognitive Disorders Extra1664-54642016-04-016114214910.1159/000444788444788Cerebrospinal Fluid TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis Patients with and without the C9ORF72 Hexanucleotide ExpansionAnna JunttilaMari KuvajaPäivi HartikainenMaritta SiloahoSeppo HelisalmiVirpi MoilanenAnna KiviharjuLilja JanssonPentti J. TienariAnne Marja RemesSanna-Kaisa HerukkaBackground: 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 C9ORF72 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 C9ORF72 expansion carrier status affects these variables. Methods: The patient cohort consisted of 90 clinically well-characterized FTLD (n = 69) and ALS (n = 21) patients. There were 30 patients with the C9ORF72 expansion and 60 patients without the expansion. CSF TDP-43, Aβ1-42, t-tau, and phospho-tau levels were measured using commercial ELISA kits. Results: There was no difference in CSF TDP-43 levels between the C9ORF72 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 C9ORF72 expansion carrier status. Males had significantly higher TDP-43 levels than females (p = 0.008 in the total cohort). Conclusion: CSF TDP-43 does not seem to distinguish the C9ORF72 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.http://www.karger.com/Article/FullText/444788Frontotemporal lobar degenerationFrontotemporal dementiaAmyotrophic lateral sclerosisTDP-43Cerebrospinal fluidC9ORF72BiomarkerELISA |
| spellingShingle | Anna Junttila Mari Kuvaja Päivi Hartikainen Maritta Siloaho Seppo Helisalmi Virpi Moilanen Anna Kiviharju Lilja Jansson Pentti J. Tienari Anne Marja Remes Sanna-Kaisa Herukka Cerebrospinal Fluid TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis Patients with and without the C9ORF72 Hexanucleotide Expansion Dementia and Geriatric Cognitive Disorders Extra Frontotemporal lobar degeneration Frontotemporal dementia Amyotrophic lateral sclerosis TDP-43 Cerebrospinal fluid C9ORF72 Biomarker ELISA |
| title | Cerebrospinal Fluid TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis Patients with and without the C9ORF72 Hexanucleotide Expansion |
| title_full | Cerebrospinal Fluid TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis Patients with and without the C9ORF72 Hexanucleotide Expansion |
| title_fullStr | Cerebrospinal Fluid TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis Patients with and without the C9ORF72 Hexanucleotide Expansion |
| title_full_unstemmed | Cerebrospinal Fluid TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis Patients with and without the C9ORF72 Hexanucleotide Expansion |
| title_short | Cerebrospinal Fluid TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis Patients with and without the C9ORF72 Hexanucleotide Expansion |
| title_sort | cerebrospinal fluid tdp 43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis patients with and without the c9orf72 hexanucleotide expansion |
| topic | Frontotemporal lobar degeneration Frontotemporal dementia Amyotrophic lateral sclerosis TDP-43 Cerebrospinal fluid C9ORF72 Biomarker ELISA |
| url | http://www.karger.com/Article/FullText/444788 |
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