Plasma NFL, GFAP, sTREM2, pTau231, and clinical severity in progressive supranuclear palsy

This study aimed to investigate four plasma markers, pTau231, sTREM2, neurofilament light chain (NFL), and glial fibrillary acidic protein (GFAP), in relation to disease severity in a Korean cohort of progressive supranuclear palsy (PSP).

Baseline data from patients with probable PSP enrolled in the SCANPSP cohort (NCT05579301) were compared with those of age-matched healthy controls (HC). Four plasma markers measured using the Simoa method, clinical findings, and volumetric 3 T MRI were investigated.

This study included 68 patients with PSP and 30 HC. Group level difference were found in NFL, correlating with the PSP-rating scale (r = 0.48, p = 2.0·10^-4) and global cognitive scores (r = -0.34, p = 0.0061 for Mini-Mental Status Exam: r = -0.32, p = 0.0088 for Montreal Cognitive Assessment). Intercorrelations between NFL, pTau231, and GFAP were observed in patients with PSP but no intercorrelations in HC. The combination of pTau231, NFL, and GFAP yielded the highest ability to distinguish the PSP-Richarson syndrome (PSP-RS) from the PSP-subcortical, with an area under the curve of 0.80. The gray matter voxel-wise correlation of whole patient data showed that NFL correlated with third ventricle enlargement and frontal/cingulate atrophy, whereas sTREM2 correlated with third ventricle and thalamic volumes. White matter analyses revealed that the supplementary motor area and vermis correlated with NFL in whole PSP. In PSP-RS group, the superior frontal gyrus was associated with NFL, and the cerebellar crus with sTREM2.

This study demonstrated the feasibility of using four plasma markers simultaneously to determine PSP disease severity. To verify these findings, longitudinal analyses are necessary.