APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline.

The BBB breakdown in HC and PHG in APOE4 carriers, but not APOE3 homozygotes, remained a highly significant predictor of cognitive impairment after statistically controlling for age, sex, education, CSF Aβ and pTau status, and HC and PHG volumes, as shown by the estimated marginal means from the analysis of covariance (ANCOVA) models ( Fig. 1l , m ), and confirmed by logistic regression models ( Supplementary Information Table 1 ).

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