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

Oskar Hansson, Alexander F. Santillo, Lieke H. Meeter, Karin Nilsson, Maria Landqvist Waldö, Christer Nilsson, Kaj Blennow, John C. van Swieten, Shorena Janelidze

Research output: Contribution to journalArticleAcademicpeer-review

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 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.
Original languageEnglish
Pages (from-to)863-872
JournalAnnals of Clinical and Translational Neurology
Volume6
Issue number5
DOIs
Publication statusPublished - 2019

Cite this

Hansson, O., Santillo, A. F., Meeter, L. H., Nilsson, K., Landqvist Waldö, M., Nilsson, C., ... Janelidze, S. (2019). CSF placental growth factor – a novel candidate biomarker of frontotemporal dementia. Annals of Clinical and Translational Neurology, 6(5), 863-872. https://doi.org/10.1002/acn3.763
Hansson, Oskar ; Santillo, Alexander F. ; Meeter, Lieke H. ; Nilsson, Karin ; Landqvist Waldö, Maria ; Nilsson, Christer ; Blennow, Kaj ; van Swieten, John C. ; Janelidze, Shorena. / CSF placental growth factor – a novel candidate biomarker of frontotemporal dementia. In: Annals of Clinical and Translational Neurology. 2019 ; Vol. 6, No. 5. pp. 863-872.
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title = "CSF placental growth factor – a novel candidate biomarker of frontotemporal dementia",
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 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.",
author = "Oskar Hansson and Santillo, {Alexander F.} and Meeter, {Lieke H.} and Karin Nilsson and {Landqvist Wald{\"o}}, Maria and Christer Nilsson and Kaj Blennow and {van Swieten}, {John C.} and Shorena Janelidze",
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Hansson, O, Santillo, AF, Meeter, LH, Nilsson, K, Landqvist Waldö, M, Nilsson, C, Blennow, K, van Swieten, JC & Janelidze, S 2019, 'CSF placental growth factor – a novel candidate biomarker of frontotemporal dementia' Annals of Clinical and Translational Neurology, vol. 6, no. 5, pp. 863-872. https://doi.org/10.1002/acn3.763

CSF placental growth factor – a novel candidate biomarker of frontotemporal dementia. / Hansson, Oskar; Santillo, Alexander F.; Meeter, Lieke H.; Nilsson, Karin; Landqvist Waldö, Maria; Nilsson, Christer; Blennow, Kaj; van Swieten, John C.; Janelidze, Shorena.

In: Annals of Clinical and Translational Neurology, Vol. 6, No. 5, 2019, p. 863-872.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - CSF placental growth factor – a novel candidate biomarker of frontotemporal dementia

AU - Hansson, Oskar

AU - Santillo, Alexander F.

AU - Meeter, Lieke H.

AU - Nilsson, Karin

AU - Landqvist Waldö, Maria

AU - Nilsson, Christer

AU - Blennow, Kaj

AU - van Swieten, John C.

AU - Janelidze, Shorena

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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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UR - https://www.ncbi.nlm.nih.gov/pubmed/31139684

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DO - 10.1002/acn3.763

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JO - Annals of Clinical and Translational Neurology

JF - Annals of Clinical and Translational Neurology

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