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

Ann Clin Transl Neurol. 2019 Mar 29;6(5):863-872. doi: 10.1002/acn3.763. eCollection 2019 May.

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.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnosis
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers
  • Cohort Studies
  • Female
  • Frontotemporal Dementia / diagnosis*
  • Frontotemporal Dementia / physiopathology*
  • Humans
  • Male
  • Middle Aged
  • Placenta Growth Factor / cerebrospinal fluid*
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • PGF protein, human
  • tau Proteins
  • Placenta Growth Factor

Grant support

This work was funded by Skåne Research Hospital research funds grant ; Alzheimer Nederland grant ; European Research Council grant ; Swedish Research Council grant ; Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University grant ; Crafoord Foundation grant ; Swedish Brain Foundation grant ; Swedish Alzheimer Foundation grant ; Torsten Söderberg Foundation grant ; Greta and Johan Kock Foundation grant ; Koch's Foundation grant ; Swedish Society for Medical Research grant ; Bente Rexed Gersteds Foundation for Brain Research grant ; Swedish federal government under the ALF agreement grant ; European Joint Programme – Neurodegenerative Disease Research grant ; Netherlands Organisation for Health Research and Development grant ; Dioraphte Foundation grants RiMod‐FTD 733051024, Memorabel 733050103, and WE.09‐2014‐04.