Table 3

CSF neuronal injury markers: tau, neurofilament light chain (NF-L) and glial fibrillary acidic protein (GFAP) in parkinsonian disorders

Research groupsParticipantsAnalyteMethodMain findings
Kang et al21PD n=39 (drug-naïve patients), HC n=63t-tau, p-tauBead-based multi-analyte assay (Luminex)Decrease in t-tau+p-tau in PD vs controls
Luk et al64PDD n=11, PSP n=44, CBS n=22, AD n=11, controls n=343R/4R isoformsImmuno-PCR (adapted from sandwich ELISAs)
  • Decrease in 4R-tau in PSP and AD vs controls

  • Lower 4R-tau in AD vs PDD

  • -No difference in 3R-tau

Hall et al 201226PD n=90, PDD n=33, DLB n=70, PSP n=45, CBD n=12, MSA n=48, AD n=48, controls n=107t-tau, p-tau
Bead-based multi-analyte assay (Luminex)
  • Increased t-and p-tau in AD vs DLB+PDD

  • NF-L differentiates PD from atypical parkinsonism

Bech et al32PD n=22, PDD n=3, DLB n=11, MSA n=10, PSP n=20, CBD n=3NF-LELISA
  • Higher NF-L levels in atypical parkinsonian disorders vs PD

  • No difference between parkinsonian groups

Andersson et al34DLB n=47, PDD n=17, AD n=150t-tau, p-tauELISAIncreased t-tau in DLB vs PDD
Shi et al22Discovery cohort: PD n=126, MSA n=32, AD n=50, controls n=137
Validation cohort: PD n=83
t-tau, p-tauBead-based multi-analyte assay (Luminex)
  • -Decrease in PD vs to controls

  • -Decrease in PD+MSA vs AD

Parnetti et al 201127PD n=38, DLB n=32, AD n=48, FTD n=31, controls n=32t-tau, p-tauELISA
  • Increase in AD>FTD>DLB vs PD and controls

  • No difference between PD and controls

Kuiperij et al102NA33/55
kDa tau forms
Immunoprecipitation assay and western blotting
  • Not able to detect tau form ratio

  • Suggested that 33/55 kDa bands seen are heavy and light IgG chains

Borroni et al103PSP n=18, CBS n=16, FTD n=28, controls n=2533/55
kDa tau forms
Immunoprecipitation assay and western blottingtau form ratio significantly reduced in PSP vs other groups
Constantinescu et al71PD n=10, MSA n=21, PSP n=14, CBD n=11, HC n=59
(×2 consecutive samples)
  • NF-L: normal levels in PD, elevated in MSA, PSP+CBD

  • No statistical significance overtime

  • GFAP: no difference

Montine et al28PD n=41, PDD n=11, AD n=49, HC n=150t-tau, p-tauBead-based multi-analyte assay (Luminex)
  • t-tau: no difference between parkinsonian groups

  • p-tau: reduced in PD vs HC

Süssmuth et al29PSP-RS n=20, PSP-P n=7, MSA-P n=11, MSA-C n=14, PD n=23, controls n=20t-tau, p-tau
  • p-tau/t-tau ratio lower in PSP and MSA vs PD

  • GFAP: increase in parkinsonian syndromes (no difference between disease groups)

Alves et al23PD n=109, AD n=20, HC n=36t-tau, p-tauELISANo difference between PD and controls
Ohrfelt et al30PD n=15, DLB n=15, AD n=66, controls n=55t-tau, p-tauELISANo difference between parkinsonian groups
Compta et al24PD n=20, PDD n=20, HC n=15t-tau, p-tauELISAt- and p- tau: increase in PDD vs PD and controls
Parnetti et al25PD n=20, PDD n=8, DLB n=19, AD n=23, HC n=20t-tau, p-tauELISA
  • t-tau: DLB > PDD > controls

  • p-tau: no difference between parkinsonian groups

Borroni et al65PSP n=21, CBS n=20, FTD n=44, AD n=15, PD n=10, DLB n=15, controls n=2733/55
kDa tau forms
Semiquantitative immunoprecipitation and western blottingtau forms significantly reduced in PSP vs controls and other neurodegenerative diseases
Brettschneider et al70PD n=22, MSA n=21, PSP n=21, CBD n=6, controls n=45NF-HELISAIncreased in MSA and PSP vs PD, CBD and controls
  • AD, Alzheimer's disease; CBD, corticobasal degeneration; CBS, corticobasal syndrome; CSF, cerebrospinal fluid; DLB, dementia with Lewy bodies; FTD, frontotemporal dementia; HC, healthy controls; MSA, multiple system atrophy; MSA-C, multiple system atrophy cerebellar type; MSA-P, multiple system atrophy parkinsonian type; NF_H, neurofilament heavy chain; NF-L, neurofilament light chain; PD, Parkinson's disease; PDD, Parkinson's disease dementia; PSP, progressive supranuclear palsy; PSP-P, progressive supranuclear palsy–parkinsonism; PSP-RS, progressive supranuclear palsy–Richardson's syndrome.