Β-amyloid formation, an indicative element of Alzheimer's disease (AD), is a consequence of alternative expression of enzymes involved in the cleavage of amyloid precursor protein (APP), leading to dementia in elderly populations.
A comprehensive genomic study was conducted by Dr. Wongchitrat et al. to investigate the peripheral blood markers of Alzheimer's disease. Blood samples were collected from patients with AD, and the regulation as well as genes expression of enzymes involved in APP-processing was monitored. Group of enzymes including β-site APP-cleaving enzyme 1 (BACE1), presenilin1 (PSEN1), disintegrin, metalloproteinases MMP10 (ADAM10), MMP17 (ADAM17) and NAD-dependent deacetylase sirtuin-1 were identified to have a major role in the progression of Aβ formation.
Dr. Wongchitrat used RT-PCR to monitor specific mRNA expression of healthy individuals and AD patients, whilst comparative mRNA levels were measured with respect to cognitive efficiency of participants. Interestingly, their findings at Mahidol University, Thiland, highlighted prominent variations in mRNA expression of enzymes, with BACE1 and SIRT2 as significant markers (with higher levels) in AD subjects. However, ADAM10 and SIRT1 levels were considerably lower in AD patients. Correlations were found amongst the expression of BACE1, ADAM10 and SIRT1 and cognitive performance scores.
Wongchitrat's group also measured plasma levels of most essential Aβ isoforms (Aβ40 & Aβ42), indicating the higher levels of total Aβ (Aβ40+Aβ42) and the Aβ40/Aβ42 ratio in AD subjects with low plasma Aβ42 values. Additionally, association between TMSE (first neuropsychiatric test for the standard mental status examination) and Aβ isoforms was also calculated.
The current study reports their detailed analysis on peripheral markers of Alzheimer's disease and potential role of these enzymes in Aβ synthesis, for future scholarly endeavors. The analysis of such markers will be a significant contribution to research activities designed for the monitoring, diagnosis, detection, and prognosis of Alzheimer's disease.