Open AccessCSF placental growth factor – a novel candidate biomarker of frontotemporal dementia
Author(s) -
Hansson Oskar,
Santillo Alexander F.,
Meeter Lieke H.,
Nilsson Karin,
Landqvist Waldö Maria,
Nilsson Christer,
Blennow Kaj,
Swieten John C.,
Janelidze Shorena
Publication year - 2019
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.763
Subject(s) - frontotemporal dementia , dementia , medicine , biomarker , cohort , oncology , gastroenterology , disease , biology , biochemistry
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 (Pl GF ) 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 Bio FINDER study. For validation, CSF Pl GF 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 Pl GF compared with controls ( sMCI P = 0.019; MCI ‐ AD P = 0.005; AD dementia, DLB ‐ PDD , VaD, and FTD all P < 0.001). Pl GF levels were 1.8–2.1‐fold higher in FTD than in AD , DLB ‐ PDD and VaD (all P < 0.001). Pl GF distinguished with high accuracy FTD from controls and sMCI performing better than tau/A β 42 ( AUC 0.954–0.996 versus 0.564–0.754, P < 0.001). A combination of Pl GF , tau, and A β 42 (tau/A β 42/Pl GF ) was more accurate than tau/A β 42 when differentiating FTD from a group of other dementias ( AUC 0.972 vs. 0.932, P < 0.01). Increased CSF levels of Pl GF in FTD compared with controls were corroborated in the validation cohort. Interpretation CSF Pl GF is increased in FTD compared with other dementia disorders, MCI , and healthy controls and might be useful as a diagnostic biomarker of FTD .