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

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 ( = 27), Alzheimer disease (AD) dementia ( = 75), DLB or PDD ( = 47), subcortical vascular dementia (VaD,  = 33), mild cognitive impairment that later converted to AD (MCI-AD,  = 34), stable MCI (sMCI,  = 62), and 50 cognitively healthy controls from the Swedish BioFINDER study. For validation, CSF PlGF was measured in additional independent cohort of FTD patients ( = 22) and controls ( = 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  = 0.019; MCI-AD  = 0.005; AD dementia, DLB-PDD, VaD, and FTD all  < 0.001). PlGF levels were 1.8-2.1-fold higher in FTD than in AD, DLB-PDD and VaD (all  < 0.001). PlGF distinguished with high accuracy FTD from controls and sMCI performing better than tau/A42 (AUC 0.954-0.996 versus 0.564-0.754,  < 0.001). A combination of PlGF, tau, and A42 (tau/A42/PlGF) was more accurate than tau/A42 when differentiating FTD from a group of other dementias (AUC 0.972 vs. 0.932,  < 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.