Association of hemolytic biomarkers with elevated circulating NFL and pTau in SCD. Biorepository steady state plasma samples were analyzed for hemolytic and neurocognitive biomarkers using enzyme-linked immunosorbent or colorimetric assays following manufacturer’s instructions. (A) Level of plasma NFL is elevated in patients with SCD (SS) compared to age-matched nonsickle (AA) individuals (AA, n = 12; SS, n = 24). (B) Level of plasma pTau217 is also elevated in patients with SCD (SS) as compared to AA individuals. (C) Association of plasma NFL and pTau217 in individuals with SCD (n = 24) in logarithmic scale. (D-E) Plasma NFL and pTau217 in AA and SS mice (n = 15; M, 6; F, 9) at baseline and following heme challenge in SS mice (SSH; n = 15; M, 6; F, 9). Unpaired t test for panels A-B; 1-way analysis of variance (ANOVA) for panels D-E. ∗P < .05, ∗∗∗P < .001. F, female mice; M, male mice.