Alterations in the Expression of Amyloid Precursor Protein Cleaving Enzymes mRNA in Alzheimer Peripheral Blood.

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia in elderly populations. Changes in the expression of the Amyloid Precursor Protein (APP)-cleaving enzymes directly affect the formation of Amyloid Beta (Aß) plaques, a neuropathological hallmark of AD. OBJECTIVE: We used peripheral blood from AD patients to investigate the expression of genes related to APP-processing [(ß-site APP-cleaving enzyme 1 (BACE1), presenilin1 (PSEN1), and a disintegrin and metalloproteinase family 10 (ADAM10) and 17 (ADAM17)] and the epigenetic genes sirtuin (SIRT)1-3, which regulate Aß production. METHOD: Real-time polymerase chain reactions were performed to determine the specific mRNA levels in plasma. The mRNA levels in AD patients were compared to those in healthy persons and assessed in relation to the subjects' cognitive performance. RESULTS: BACE1 mRNA level in AD subjects was significantly higher than those of healthy controls, whereas ADAM10 level was significantly lower in the AD subjects. The SIRT1 level was significantly decreased, while that of SIRT2 was increased in AD subjects and elderly controls compared to levels in healthy young control. In addition, correlations were found between the expression levels of BACE1, ADAM10 and SIRT1 and cognitive performance scores. Total Aß (Aß40+Aß42) levels and the Aß40/Aß42 ratio were significantly increased in the AD subjects, whereas decrease in plasma Aß42 was found in AD subjects. There was a negative correlation between Aß40 or total Aß and Thai Mental State Examination (TMSE) while there was no correlation between Aß40/Aß42 ratio or Aß42 and TMSE. CONCLUSION: The present findings provide evidence and support for the potential roles of these enzymes that drive Aß synthesis and for epigenetic regulation in AD progression and development, which can possibly be considered peripheral markers of AD.