| Novel CSF biomarkers for frontotemporal lobar degenerations. | |
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MedLine Citation:
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PMID: 21048198 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To identify antemortem CSF diagnostic biomarkers that can potentially distinguish between the 2 main causes of frontotemporal lobar degeneration (FTLD), i.e., FTLD with TDP-43 pathology (FTLD-TDP) and FTLD with tau pathology (FTLD-tau). METHODS: CSF samples were collected antemortem from 23 patients with FTLD with known pathology to form a autopsy cohort as part of a comparative biomarker study that additionally included 33 living cognitively normal subjects and 66 patients with autopsy-confirmed Alzheimer disease (AD). CSF samples were also collected from 80 living patients clinically diagnosed with frontotemporal dementia (FTD). Levels of 151 novel analytes were measured via a targeted multiplex panel enriched in neuropeptides, cytokines, and growth factors, along with levels of CSF biomarkers for AD. RESULTS: CSF levels of multiple analytes differed between FTLD-TDP and FTLD-tau, including Fas, neuropeptides (agouti-related peptide and adrenocorticotropic hormone), and chemokines (IL-23, IL-17). Classification by random forest analysis achieved high sensitivity for FTLD-TDP (86%) with modest specificity (78%) in the autopsy cohort. When the classification algorithm was applied to a living FTD cohort, semantic dementia was the phenotype with the highest predicted proportion of FTLD-TDP. When living patients with behavioral variant FTD were examined in detail, those predicted to have FTLD-TDP demonstrated neuropsychological differences vs those predicted to have FTLD-tau in a pattern consistent with previously reported trends in autopsy-confirmed cases. CONCLUSIONS: Clinical cases with FTLD-TDP and FTLD-tau pathology can be potentially identified antemortem by assaying levels of specific analytes that are well-known and readily measurable in CSF. |
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Authors:
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W T Hu; A Chen-Plotkin; M Grossman; S E Arnold; C M Clark; L M Shaw; L McCluskey; L Elman; H I Hurtig; A Siderowf; V M-Y Lee; H Soares; J Q Trojanowski |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-11-03 |
Journal Detail:
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Title: Neurology Volume: 75 ISSN: 1526-632X ISO Abbreviation: Neurology Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-07 Completed Date: 2011-01-07 Revised Date: 2011-12-21 |
Medline Journal Info:
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Nlm Unique ID: 0401060 Medline TA: Neurology Country: United States |
Other Details:
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Languages: eng Pagination: 2079-86 Citation Subset: AIM; IM |
Affiliation:
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Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia 19104-4283, USA. trojanow@mail.med.upenn.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adrenocorticotropic Hormone
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cerebrospinal fluid Aged Alzheimer Disease / cerebrospinal fluid Biological Markers / cerebrospinal fluid* Cohort Studies DNA-Binding Proteins / metabolism* Female Frontotemporal Lobar Degeneration / cerebrospinal fluid*, complications Humans Interleukin-17 / cerebrospinal fluid Male Mental Status Schedule Middle Aged Neuropsychological Tests Statistics, Nonparametric Tauopathies / cerebrospinal fluid*, complications |
| Grant Support | |
ID/Acronym/Agency:
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1 U01 AG 024904-05/AG/NIA NIH HHS; 1P01 AG-19724-07/AG/NIA NIH HHS; 1RC 2AG-036535/AG/NIA NIH HHS; AG024904/AG/NIA NIH HHS; AG15116/AG/NIA NIH HHS; AG17586/AG/NIA NIH HHS; NS44266/NS/NINDS NIH HHS; NS53488/NS/NINDS NIH HHS; P01 AG 09215-20/AG/NIA NIH HHS; P01 AG17586-10/AG/NIA NIH HHS; P30 AG 10124-18/AG/NIA NIH HHS; P30-AG 009215-19/AG/NIA NIH HHS; P30AG036468/AG/NIA NIH HHS; P50 NS053488/NS/NINDS NIH HHS; P50 NS053488-01/NS/NINDS NIH HHS; P50 NS053488-02/NS/NINDS NIH HHS; R01NS065087/NS/NINDS NIH HHS; R43NS0636071/NS/NINDS NIH HHS; RC1AG035427/AG/NIA NIH HHS; RC2NS069368/NS/NINDS NIH HHS; U10NS0444451/NS/NINDS NIH HHS; U10NS044451-023/NS/NINDS NIH HHS; UO1 AG029213-01/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 0/DNA-Binding Proteins; 0/Interleukin-17; 0/protein TDP-43; 9002-60-2/Adrenocorticotropic Hormone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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