Investigation of mRNA levels of JUN, FOS, RELA transcription factors and PCK2 protein level in Alzheimer's disease

The Amyloid Precursor Protein (APP) emerges as a significant player in the pathogenesis of Alzheimer's Disease (AD). The Amyloid Precursor Protein (APP) stands out as a significant player in the pathogenesis of Alzheimer's Disease (AD). It interacts with various transcription factors (TFs). Our protein-protein interaction analyses revealed potential interactions between APP and the transcription factors Jun, Fos, and RELA. Additionally, these three TFs regulate the expression of PCK2. To investigate further, we examined the relative mRNA levels of Jun, Fos, and RELA in the blood samples of patients with Alzheimer's Disease (AD), Mild Cognitive Impairment (MCI), and Frontotemporal Dementia (FTD), as well as in cognitively healthy individuals, using real-time polymerase chain reaction (PCR). Furthermore, the levels of PCK2 in the cerebrospinal fluid (CSF) of the participants were measured using ELISA. According to the results of this experimental set, an increase in the expression of the Fos TF was observed in AD compared to healthy control individuals, which was statistically significant. However, no significant relationship was detected in the other groups. Additionally, while in the FTD patient group, a decrease in CSF PCK2 levels correlated with an increase in Aβ1-42 levels, in the AD group, a positive correlation was found between PCK2 protein and Aβ1-42. Studies indicate that as Alzheimer's Disease progresses, neuronal stress and damage in the brain increase, potentially triggering the activation of c-Fos. PCK2, regulated by the investigated TFs, plays a critical role in cellular energy metabolism and processes such as gluconeogenesis. Especially noteworthy is the contrasting correlation pattern of PCK2 protein with Aβ1-42, showing a negative correlation in the FTD patient group but a positive correlation in the AD group. This finding may shed light on the differences in glucose metabolism and mitochondrial dysfunction between these two neurodegenerative diseases.