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 (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.