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CSF placental growth factor – a novel candidate biomarker of frontotemporal dementia

Hansson, Oskar LU ; Santillo, Alexander F. LU ; Meeter, Lieke H.; Nilsson, Karin LU ; Landqvist Waldö, Maria LU ; Nilsson, Christer LU ; Blennow, Kaj LU ; van Swieten, John C. and Janelidze, Shorena LU (2019) In Annals of Clinical and Translational Neurology 6(5). p.863-872
Abstract

Objective: Diagnosis of frontotemporal dementia (FTD) is complicated by the overlap of clinical symptoms with other dementia disorders. Development of robust fluid biomarkers is critical to improve the diagnostic work-up of FTD. Methods: CSF concentrations of placental growth factor (PlGF) were measured in the discovery cohort including patients with FTD (n = 27), Alzheimer disease (AD) dementia (n = 75), DLB or PDD (n = 47), subcortical vascular dementia (VaD, n = 33), mild cognitive impairment that later converted to AD (MCI-AD, n = 34), stable MCI (sMCI, n = 62), and 50 cognitively healthy controls from the Swedish BioFINDER study. For validation, CSF PlGF was measured in additional independent cohort of FTD patients (n = 22) and... (More)

Objective: Diagnosis of frontotemporal dementia (FTD) is complicated by the overlap of clinical symptoms with other dementia disorders. Development of robust fluid biomarkers is critical to improve the diagnostic work-up of FTD. Methods: CSF concentrations of placental growth factor (PlGF) were measured in the discovery cohort including patients with FTD (n = 27), Alzheimer disease (AD) dementia (n = 75), DLB or PDD (n = 47), subcortical vascular dementia (VaD, n = 33), mild cognitive impairment that later converted to AD (MCI-AD, n = 34), stable MCI (sMCI, n = 62), and 50 cognitively healthy controls from the Swedish BioFINDER study. For validation, CSF PlGF was measured in additional independent cohort of FTD patients (n = 22) and controls (n = 18) from the Netherlands. Results: In the discovery cohort, MCI, MCI-AD, AD dementia, DLB-PDD, VaD, and FTD patients all showed increased CSF levels of PlGF compared with controls (sMCI P = 0.019; MCI-AD P = 0.005; AD dementia, DLB-PDD, VaD, and FTD all P < 0.001). PlGF levels were 1.8–2.1-fold higher in FTD than in AD, DLB-PDD and VaD (all P < 0.001). PlGF distinguished with high accuracy FTD from controls and sMCI performing better than tau/Aβ42 (AUC 0.954–0.996 versus 0.564–0.754, P < 0.001). A combination of PlGF, tau, and Aβ42 (tau/Aβ42/PlGF) was more accurate than tau/Aβ42 when differentiating FTD from a group of other dementias (AUC 0.972 vs. 0.932, P < 0.01). Increased CSF levels of PlGF in FTD compared with controls were corroborated in the validation cohort. Interpretation: CSF PlGF is increased in FTD compared with other dementia disorders, MCI, and healthy controls and might be useful as a diagnostic biomarker of FTD.

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type
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publication status
published
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in
Annals of Clinical and Translational Neurology
volume
6
issue
5
pages
10 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:85066108699
ISSN
2328-9503
DOI
10.1002/acn3.763
language
English
LU publication?
yes
id
60556abe-5650-4395-896f-3b380e1b67b3
date added to LUP
2019-06-11 14:39:51
date last changed
2019-07-02 04:47:48
@article{60556abe-5650-4395-896f-3b380e1b67b3,
  abstract     = {<p>Objective: Diagnosis of frontotemporal dementia (FTD) is complicated by the overlap of clinical symptoms with other dementia disorders. Development of robust fluid biomarkers is critical to improve the diagnostic work-up of FTD. Methods: CSF concentrations of placental growth factor (PlGF) were measured in the discovery cohort including patients with FTD (n = 27), Alzheimer disease (AD) dementia (n = 75), DLB or PDD (n = 47), subcortical vascular dementia (VaD, n = 33), mild cognitive impairment that later converted to AD (MCI-AD, n = 34), stable MCI (sMCI, n = 62), and 50 cognitively healthy controls from the Swedish BioFINDER study. For validation, CSF PlGF was measured in additional independent cohort of FTD patients (n = 22) and controls (n = 18) from the Netherlands. Results: In the discovery cohort, MCI, MCI-AD, AD dementia, DLB-PDD, VaD, and FTD patients all showed increased CSF levels of PlGF compared with controls (sMCI P = 0.019; MCI-AD P = 0.005; AD dementia, DLB-PDD, VaD, and FTD all P &lt; 0.001). PlGF levels were 1.8–2.1-fold higher in FTD than in AD, DLB-PDD and VaD (all P &lt; 0.001). PlGF distinguished with high accuracy FTD from controls and sMCI performing better than tau/Aβ42 (AUC 0.954–0.996 versus 0.564–0.754, P &lt; 0.001). A combination of PlGF, tau, and Aβ42 (tau/Aβ42/PlGF) was more accurate than tau/Aβ42 when differentiating FTD from a group of other dementias (AUC 0.972 vs. 0.932, P &lt; 0.01). Increased CSF levels of PlGF in FTD compared with controls were corroborated in the validation cohort. Interpretation: CSF PlGF is increased in FTD compared with other dementia disorders, MCI, and healthy controls and might be useful as a diagnostic biomarker of FTD.</p>},
  author       = {Hansson, Oskar and Santillo, Alexander F. and Meeter, Lieke H. and Nilsson, Karin and Landqvist Waldö, Maria and Nilsson, Christer and Blennow, Kaj and van Swieten, John C. and Janelidze, Shorena},
  issn         = {2328-9503},
  language     = {eng},
  number       = {5},
  pages        = {863--872},
  publisher    = {Wiley-Blackwell},
  series       = {Annals of Clinical and Translational Neurology},
  title        = {CSF placental growth factor – a novel candidate biomarker of frontotemporal dementia},
  url          = {http://dx.doi.org/10.1002/acn3.763},
  volume       = {6},
  year         = {2019},
}