Dysregulation of Cell Cycle Regulating Proteins in Peripheral Lymphocytes from the Patients with Alzheimer's Disease

Chung, Sung Ho; Kwon, Young Ah; Kim, Hyeran; Shin, Ji Young; Kim, Doh Kwan

Abstract

OBJECTIVE
Extensive neuronal death occurring in the Alzheimer's disease (AD) may be related with the apoptosis. Recent studies have suggested that regulatory failure of cell cycle appeared to be very early event of AD pathogenesis in neuronal cells as well as in peripheral lymphocytes. We compared the change of cyclin dependent kinases (Cdks), which is related with G1/S phase transition in the cell cycle, between AD patients and normal controls using peripheral lymphocytes. METHODS: We obtained Cdks from peripheral lymphocytes of 37 AD patients and 18 age-matched normal subjects. Cells in first culture were considered to be G-zero (G0) cells. We measured Cdk2, Cdk4, and Cdk6 at baseline (T0). Thereafter, we observed Cdks 24 hours later after using PHA (phytohemaglutinin) (N24). Meanwhile, we observed Cdks 24 hours later again with rapamycin treatment (T24). RESULTS: At baseline (T0), Cdk2 and Cdk6 were increased in AD patients compared to the control group (p< 0.001, p=0.038, respectively). Cdk2 was increased in AD patients more than control group after using PHA (T24, p=0.007). After rapamycin treatment for 24 hours (N24), Cdk2, Cdk4, and Cdk6 were increased in the patients compared to the controls (p=0.002, p=0.022, p=0.011, respectively). CONCLUSION: This results showed that the cell cycle regulating proteins in AD patients, which are related with G1/S phase transition, were increased in peripheral lymphocytes compared to those in normal controls. We provide the clue which demonstrate the cell cycle dysregulation in the patients with Alzheimer's disease.