This genome-wide gene expression profiling study of a large cohort of AD and normal aging brains revealed large groups of genes that vary as a function of age and disease status. When the hundreds of gene expression values contained in each of these sets are converted into a single quantitative trait, new molecular biomarkers of biological aging and disease progression emerge. The transcriptional profiles of AD brains were profoundly different from those in non-demented individuals, with thousands of genes differing in their levels of expression between the two cohorts. To reduce the complexity of the observed changes, we focused on key gene expression patterns that explained the most variability across the cohorts. We demonstrated that the most significant pattern in terms of variance explained both within and between AD and non-demented cohorts was BioAge, a biomarker of the level of biological aging in the brain. BioAge captured the extent of gradual molecular changes in the normal aging brain by averaging the gene expression changes associated with a multitude of synchronous physiological events. BioAge can be accurately and reliably assigned to
