Age-related changes in gene expression are accelerated in Alzheimer's disease

Abstract

In the normal brain, age is associated with changes in gene expression. Age is also a prominent risk factor for Alzheimer's disease (AD), where clinical features are similar to age-related decreases in cognitive performance. We hypothesized that some age-related changes in gene expression are accelerated in AD patients. To study this, we selected 10 candidate genes earlier shown by microarray analysis to be differentially expressed in AD (Emilsson et al., [2006] Neurobiol Dis 21:618-625). Using real-time PCR analysis and a control based statistical model, we investigated age-related changes in mRNA levels in a large collection of human brain postmortem tissues from AD patients and controls. Our results demonstrate that the age-related changes in gene expression are manifested earlier in AD. Furthermore, five of the genes (ITPKB, RGS4, RAB3A, STMN1, SYNGR3) have in common an involvement in neuronal calcium dependent signaling, a cellular process previously related to both AD and aging. These observations suggest that coordinated transcriptional changes associated with ageing and calcium homeostasis in the human brain are accelerated in patients with AD. Our results point to the possibility that the activity of these genes can be used in the future as a palette of biomarkers for predicting disease risk in young individuals.