Peripheral blood mononuclear cells from mild cognitive impairment patients show deregulation of Bax and Sod1 mRNAs

Abstract

Elevated oxidative stress-induced apoptosis has been found in peripheral cells from patients with Alzheimer's disease (AD). Furthermore, treatment of lymphocytes from AD patients, with Aβ 1–42 and H 2O 2 results in enhanced apoptosis. Mild cognitive impairment (MCI), a clinical condition between normal aging and AD, shares with AD a similar pattern of peripheral markers of oxidative stress. In this study we investigated spontaneous and H 2O 2-induced oxidative stress and apoptosis levels in peripheral blood mononuclear cells (PBMCs) from MCI and AD patients, as well as from Parkinson's disease (PD) patients without cognitive impairment or age-matched healthy control. Sod1 mRNA levels were studied to analyse the anti-oxidative pathway, while Bax and Bcl-2 mRNAs levels and PARP protein cleavage were monitored to study apoptosis. We found that the expression of Sod1 and Bax mRNAs was statistically higher in both MCI and AD patients compared to controls or PD subjects. Since Bcl-2 mRNA level was not different among groups, the Bax/Bcl-2 ratio was statistically higher in AD and MCI patients. PARP cleavage was also enhanced in PBMCs from MCI and AD individuals and this finding was associated with a higher level of spontaneous apoptosis. Interestingly, exposure to H 2O 2 induced a significant decrease of Bcl-2 mRNA transcript, while Sod1 and Bax mRNAs levels were unchanged in PBMCs derived from MCI and AD patients. In conclusion, our results show that Bax and Sod1 mRNA levels are altered in PBMCs from both MCI and AD patients and indicate these changes as potential biomarkers in the early diagnosis of AD.