Extended Data Figure 5. Regional blood-brain barrier (BBB) breakdown Ktrans increases with CDR independent of CSF Aβ and tau and vascular risk factors (VRFs), and relates to sPDGFRβ only in hippocampal gray matter regions.

(a-b) An increase in Ktrans values in the hippocampus (HC), parahippocampal gyrus (PHC) and CA1, CA3 and dentate gyrus (DG) hippocampus subfields, with increasing CDR (a), but not in other brain regions including superior frontal cortical gyrus (Sup Front) and inferior temporal cortical gyrus (Inf Temp), white matter regions including subcortical white matter fibers (white matter, WM), corpus callosum (CC), and internal capsule (IC), and deep gray matter regions including thalamus (Thal), caudate nucleus (Caud) and striatum (b). (c-d) Additional brain regions showed no significant differences in Ktrans BBB permeability values in individuals with CDR 0 and CDR 0.5, regardless of CSF Aβ42 (c) or pTau (d) status. (e-f) VRFs burden does not influence an increase in the Ktrans BBB permeability values with increasing CDR in the HC, PHC, and hippocampus subfields (i.e., CA1, CA3, DG) (e), and no change in the Ktrans BBB permeability values in other brain regions (f). See Supplementary Table 1 for the list of VRFs. Panels a-f support Figure 1 g-k. (g-j) CSF sPDGFRβ is associated with BBB breakdown measured by neuroimaging in hippocampal gray matter regions (g-h), but not in WM regions (i-j); supports Figures 1 and 3. Panels a-f: Box-and-whisker plot lines indicate median values, boxes indicate interquartile range and whiskers indicate minimum and maximum values. Significance tests after FDR correction from ANCOVAs. Panels g-j: Statistical significance determined by Pearson correlation; r = Pearson correlation coefficient. Brackets denote sample size (n) in each analysis; applies to all regions within each panel.