Cell cycle regulation distinguishes lymphocytes from sporadic and familial Alzheimer's disease patients

Cell cycle (CC) reactivation in neurons seems to underlie the development of Alzheimer's disease (AD). We analyzed whether CC alterations can be detected in immortalized lymphocytes from patients with the sporadic and the familial form of AD (SAD and FAD). Real-time polymerase chain reaction (PCR)-arrays, immunoblotting, and flow cytometry demonstrated differences in the regulation of G1/S phases between SAD lymphocytes and cells from nondemented subjects, as well as between SAD and FAD cells. SAD compared to FAD lymphocytes showed differences in expression profiles of the 90 CC genes, and a marked increase in the level of the p21 protein, which promotes G1-arrest. Accordingly, SAD but not FAD cells had a prolonged G1-phase. γ-secretase inhibition did not change the CC profiles of the cell lines. These data show that SAD involves a prolongation of the G1 phase driven by p21 pathway, which is not activated in FAD cells. Thus, the mechanism in SAD differs from FAD. Moreover, disturbances of the CC in lymphocytes have a potential diagnostic value.