Novel CSF biomarkers for frontotemporal lobar degenerations.
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 2...
| Publicado en: | Neurology Vol. 75; no. 23; pp. 2079 - 2087 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Lippincott Williams & Wilkins
12/7/2010
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104963818&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104963818 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00283878 NRO jtl: Neurology issn: 00283878 maglogo: N pubinfo: dt: 12/7/2010 vid: 75 iid: 23 pid: 433 pub: Lippincott Williams & Wilkins place: Baltimore, Maryland artinfo: ui: 104963818 104963818 NLM21048198 2010879063 10.1212/WNL.0b013e318200d78d NLM21048198 PMC2995537 104963818 ppf: 2079 ppct: 8 formats: tig: atl: Novel CSF biomarkers for frontotemporal lobar degenerations. aug: au: Hu WT Chen-Plotkin A Grossman M Arnold SE Clark CM Shaw LM McCluskey L Elman L Hurtig HI Siderowf A Lee VM Soares H Trojanowski JQ Hu, W T Chen-Plotkin, A Grossman, M Arnold, S E Clark, C M Shaw, L M McCluskey, L affil: Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia 19104-4283, USA sug: subj: Biological Markers Cerebrospinal Fluid Proteins Metabolism Dementia Cerebrospinal Fluid Neurodegenerative Diseases Cerebrospinal Fluid Adrenocorticotropic Hormone Cerebrospinal Fluid Aged Alzheimer's Disease Cerebrospinal Fluid Prospective Studies Female Dementia Complications Human Interleukins Cerebrospinal Fluid Male Psychological Tests Middle Age Neuropsychological Tests Nonparametric Statistics Neurodegenerative Diseases Complications Aged: 65+ years Middle Aged: 45-64 years Female Male ab: 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. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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