TABLE 1.
Main findings of studies evaluating CSF and blood NfL in prion disease.
| Country of studied population | Examined biofluid | Assay | N according to prion disease form | N according to non-prion disease | AUC (cutoff)* sCJD vs. Controls | AUC (cutoff)* sCJD vs. non-prion | Other significant findings | |
| Steinacker et al. (2016) | Germany | CSF, Blood | CSF: ELISA (IBL) Blood: Simoa | 42 CJD (39 definite): 33 sCJD, 9 gCJD, 1 GSS (pre-symp) | 20 dementia patients | CSF: 0.949 (>2,156 pg/ml) Blood: 0.959 (>44.7 pg/ml) | Elevated CSF NfL in one pre-symptomatic GSS case | |
| Kovacs et al. (2017) | Austria | CSF, Blood | CSF: ELISA (Uman Dia.) Blood: Simoa | 86 definite CJD: 65 sCJD, 21 gCJD | 46 non-prion RPDs (all definite) | CSF: 0.979 Blood: 0.992 | CSF: 0.451, vs. AD 0.768. Blood: 0.497, vs. AD 0.657. | No marked differences in blood and CSF NfL among sCJD subtypes |
| Abu-Rumeileh et al. (2018b) | Italy | CSF | CSF: ELISA (IBL) | 141 prion (115 definite): 123 sCJD, 1 VPSPr 16 gCJD, 1 GSS | 73 AD (37 rp), 35 DLB (11 rp), 44 FTLD (9 rp) | CSF: 1.00 | 0.926 vs. all. Atypical prion vs. rpNDs 0.839. | Significantly higher CSF levels in the sCJD subtypes VV2 and MV2K compared to the MM(V)1 group |
| Thompson et al. (2018) | United Kingdom | Blood | Blood: Simoa | 45 sCJD (40 definite) 6 with serial samples | – | Blood: 1.00 (>44.7 pg/ml) | – | No correlation between blood NfL and rate of disease progression. Trend toward increased NfL in serial samples taken within 12 months from death |
| Zerr et al. (2018) | Germany, Poland, Spain, Portugal, Italy | CSF | CSF: ELISA (Uman Dia.) | 314 prion (257 definite) Cohort 1: 112 sCJD Cohort 2: 20 sCJD 182 gCJD | Cohort 1: 11 MCI, 88 AD, 41 DLB/PDD, 36 VaD, 11 FTD. Cohort 2: 37 MCI, 20 AD, 12 DLB/PDD, 10 VaD, 30 FTD | CSF: 0.99 (>7,000 pg/ml) | 0.90 overall (>10,500 pg/ml) >0.9 vs. AD, >0.9 vs. DLB/PDD, 0.83 vs. FTD; 0.76 vs. VaD | Prion disease: Significantly higher CSF levels in VV than in MM or MV codon 129 PRNP genotypes. Increase in NFL levels in consecutive LPs in cases with duration > 6 months. CSF NfL as a moderate prognostic marker. |
| Abu-Rumeileh et al. (2019a) | Italy | CSF | CSF: ELISA (IBL) | 103 prion (103 definite): 80 sCJD, 1 VPSPr, 22 gCJD | 109 non-prion RPDs | – | 0.693 (>1,847 pg/ml) | CSF NfL most sensitive surrogate marker in virtually all prion diseases |
| Kanata et al. (2019) | Poland, Greece | CSF | CSF: ELISA (Uman Dia.) | Cohort 1: 43 CJD Cohort 2: 21 CJD | Cohort 1: 34. Cohort 2: 29 | – | CSF: Cohort 1: 0.89 (>4,200 pg/ml), Cohort 2: 0.86 (>4,200 pg/ml) | |
| Staffaroni et al. (2019) | United States | CSF, Blood | CSF: ELISA (IBL) Blood: Simoa | 188 CJD (147 definite) | – | – | – | CSF and blood NfL associated with survival (before adjusting for covariates) |
| Abu-Rumeileh et al. (2020a) | Italy | CSF, Blood | CSF: ELISA (IBL) Blood: Simoa | 336 prion (254 definite): 275 sCJD, 1 VPSPr, 28 gCJD, 3 FFI, 3 GSS | 106 non-prion-RPDs | – | CSF: 0.646 (>1,846 pg/ml). Blood: 0.616 (>87.9 pg/ml) | CSF and blood NfL associated with survival (even after adjusting for covariates). Blood NfL as strong prognostic factor in slowly progressive prion disease |
| Thompson et al. (2020) | United Kingdom | Blood | Blood: Simoa | 231 sCJD, 14 iCJD, 17 vCJD 23 pre-symptomatic, 9 converting, 83 symptomatic PRNP mutation carriers | 31 AD, 33 FTD, 24 non-prion RPDs | Blood: 1.00 (>25.87 pg/ml) | Blood: 0.912 vs. all (>60.65 pg/ml), 0.724 vs. non-prion RPDs (>60.65 pg/ml) | Blood NfL higher in sCJD compared to genetic prion disease and vCJD. Blood NfL correlates with severity of functional impairment but not with rate of disease progression. Higher blood NfL up to 2 years before onset but not earlier in pre-symptomatic PRNP mutation carriers |
| Vallabh et al. (2020) | United States, Australia | CSF, Blood | CSF: ELISA (Uman Dia., in-house) Blood: Simoa | 27 pre-symptomatic PRNP mutation carriers 26 definite CJD: 24 sCJD, 2 gCJD | – | – | – | No difference in CSF and blood NfL between pre-symptomatic carriers and controls. No temporal increase in blood and CSF NfL in longitudinal assessments |
*Cutoffs were reported in parentheses when available.