Extended Data Fig. 2: CSF sPDGFRβ increases with CDR impairment, independent of Aβ and tau, and reflects BBB breakdown.

a–b, Site-specific analysis of CSF sPDGFRβ and the standard AD biomarkers, Aβ₄₂ and pTau, indicates an early increase in sPDGFRβ with increasing CDR at both independent clinical sites, USC (a) and Washington University (b). There were no changes in Aβ₄₂ and pTau at the USC site (a), whereas Aβ₄₂, but not pTau, was altered at the Washington University site; supports Fig. 1a–c. c–d, Site-specific analysis of CSF sPDGFRβ increases with CDR, independent of CSF Aβ₄₂ and pTau status at two independent sites, USC (c) and Washington University (d); supports Fig. 1d–f. e–f, CSF sPDGFRβ is associated with BBB breakdown. CSF sPDGFRβ positively correlates with the conventional biochemical biomarkers of BBB breakdown including the CSF/plasma albumin ratio (Q_alb) (e) and CSF fibrinogen (f); supports Figs. 1 and 3. g, CSF sPDGFRβ is increased with CDR, independent of amyloid positivity by ¹¹C-PiB-PET; supports Fig. 1d–f. h–i, No differences were observed in CSF Aβ (h) and tau (i) oligomer levels in individuals with CDR 0 versus CDR 0.5; supports Fig. 1d–f. j–k, Increases in CSF sPDGFRβ (j) and regional BBB K_trans in the HC and PHG (k) of individuals with CDR 0.5 versus CDR 0 remain significant after statistically controlling for the impact of CSF tau oligomers; supports Fig. 1d–f. a–d, g–i, The box and whisker plot lines indicate the median values, the boxes indicate the IQR, and the whiskers indicate the minimum and maximum values. a–d, g, Significance tests from ANCOVAs. e–f, Statistical significance determined by Pearson correlation coefficient (r). h–i, Significance by two-tailed Student’s t-test at α = 0.05. j–k, ANCOVA models representing estimated marginal means ± s.e.m. The brackets denote the sample size (n) in each analysis.