Associations between prognostic index scores and plasma neurofilament light in Huntington's disease

The updated development of blood-based biomarkers for Huntington’s disease

“…One retrospective cohort study firstly revealed its value of predicting clinical symptoms’ onset, which showed that baseline plasma Nfl level was a potent prognostic indicator for subsequent clinical onset within 3 years among premanifest HD patients [ 74 ]. Parkin et al further observed the association between baseline plasma Nfl level and the clinical onset within 5 years [ 78 ] and prognostic index score-derived years to onset (PIN-YTO) [ 79 ]. They also reported that the cut-point of 45.0 pg/ml for plasma Nfl distinguished premanifest participants with > 10 predicted years to onset from those ≤ 10 years [ 79 ].…”

“…Parkin et al further observed the association between baseline plasma Nfl level and the clinical onset within 5 years [ 78 ] and prognostic index score-derived years to onset (PIN-YTO) [ 79 ]. They also reported that the cut-point of 45.0 pg/ml for plasma Nfl distinguished premanifest participants with > 10 predicted years to onset from those ≤ 10 years [ 79 ]. Huntington's disease Young Adult Study (HD-YAS) showed that CSF Nfl presented a more significant association with predicted years of onset than plasma Nfl among the premanifest participants who were on average approximately 24 years from predicted onset, suggesting the predictive ability of plasma Nfl among mutation carriers far from onset may be limited compared to CSF Nfl [ 81 ].…”

Study protocol of IMAGINE-HD: Imaging iron accumulation and neuroinflammation with 7T-MRI + CSF in Huntington’s disease

“…Especially for NFL, a close correlation with disease progression and disease onset has been described ( Byrne et al, 2017 , Byrne et al, 2018 ). NFL has also been identified in blood, with the ability to predict atrophy in HD brains ( Johnson et al, 2018 ) and years to clinical onset ( Parkin et al, 2022 ). Inflammatory markers have been less studied in HD, but CSF-markers YKL-40/chitinase-3-like-protein 1 (CHI3L1) secreted by astrocytes ( Bonneh-Barkay et al, 2012 , Bonneh-Barkay et al, 2010 ) and chitotriosidase-1 (CHIT-1) secreted by activated microglia ( Rosén et al, 2014 , Varghese et al, 2013 ) are increased in many inflammatory central nervous system disorders.…”

Peripheral Biomarkers in Manifest and Premanifest Huntington’s Disease

“…Plasma NfLs were found to be a predictor of disease onset in preHD. A recent longitudinal study involving 112 patients showed a strong correlation between plasma NfL concentration and symptom onset, as assessed with the normalized prognostic index (PIN) [ 42 ]. The PIN score is a composite score that includes age, CAG repeat length, and clinical assessment, which may provide an accurate index of disease progression [ 43 ].…”