It is useful to ascribe a score based on average expression levels of all included genes as a composite measure (see Methods). We refer to the PC1 biomarker score as BioAge (biological age) based on the hypothesis that the BioAge score for an individual is a more precise and objective measure of the progression of age-related changes than chronological age. Overall, most AD samples attained much larger values of BioAge than normal samples (AUROC = 0.92). See also Table 1 for other characteristics of this biomarker. Comparison of BioAge in AD and non-demented individuals at different chronological age groups revealed a very significant difference at younger ages which decreased in chronologically older age groups. While BioAge of non-demented individuals gradually increased with age, AD patients showed consistently high levels of BioAge regardless of chronological age (Fig. 2A). The extrapolated BioAge of normal subjects would reach average AD levels at the age of 100 years. The most advanced AD brains correspond to an extrapolated age of 140 years in non-demented subjects.
