Fig. 4

The healthy ageing RNA signature in healthy human brain tissue and blood of AD patients and controls. There was robust regulation of the healthy ageing RNA signature in human brain with healthy ageing and between control subjects and subjects with AD or MCI. a The healthy ageing RNA signature was studied across brain regions in healthy individuals using BrainEac.org gene-chip resource [GEO:GSE60862]. Ten brain regions from 134 subjects representing 1231 samples were individually ranked (see “Materials and methods”) and the median sum of the ranked scores calculated. Regulation of the healthy ageing genes differed across brain regions with age, as determined by a Kruskal Wallis Test (hippocampus p = 0.00000002, putamen p = 0.00000004, thalamus p = 0.00004, temporal cortex p = 0.0001, substantia nigra p = 0.0002, frontal cortex p = 0.001, occipital cortex p = 0.001, white matter p = 0.01, medulla p = 0.06 and cerebellar cortex p = 0.51). Post hoc Mann–Whitney test, with correction for multiple comparisons (Holm), confirmed a striking ‘increase’ of the healthy ageing score in the healthy older samples (hippocampus, putamen, thalamus, substantia nigra, and the occipital, frontal, and temporal cortex regions; at least p < 0.002). b The healthy ageing RNA signature was studied in blood samples from two independently processed case–control studies of AD. In cohort 1 the control median gene score was greater (p = 0.004) than AD samples and greater (p = 0.00005) than that of the MCI samples (Wilcoxon rank sum test). In cohort 2 the median gene score of control samples was greater than that of AD samples (p = 0.009) and that of MCI samples (p = 0.003). Data are median gene score and standard error