PTAFR Exaggerates Microglia-Mediated Microenvironment via IL10-STAT3 Signaling: A Novel Perspective on Potential Biomarker and Target for AD Diagnosis and Treatment

Abstract

Background: Early diagnosis and effective intervention become the key points for delaying Alzheimer’s progression. Therefore, we aim to find new biomarkers for early diagnosis of Alzheimer (AD) by bioinformatics, and to reveal the possible mechanisms. Methods and results: GSE1297, GSE63063, and GSE110226 in the GEO database were used to screen out the differentially highly expressed genes. We found out a potential biomarker PTAFR differentially highly expressed in the brain tissue, peripheral blood and cerebrospinal fluid of AD patients. Furthermore, we found higher PTAFR level in the plasma and brain tissues of APP/PS1 mice. Simultaneously, it was uncovered that PTAFR mediated the inflammatory response to exaggerate microenvironment specially mediated by microglia through the IL10-STAT3 pathway. In addition, we also found PTAFR was a possible target for some anti-AD compounds such as EGCG, donepezil, curcumin, memantine, and Huperzine A.Conclusions: PTAFR was a potential biomarker for early AD diagnosis and treatment correlated with microglia-mediated microenvironment, and an important possible target to make novel strategy for clinical treatment and new drug discovery in AD.

Platelet activating factor: Have we been missing the forest for the trees?

“…6,11-14 PAF induces IL-6 production [15][16][17] and then IL-6 stimulates production of PAF. 18,19 PAF has also been implicated in activation of the brain-specific macrophages, microglia, 20 as well as in cancer. 21,22 PAF stimulates mast cells 23 and eosinophils, [24][25][26] and has been implicated in allergic conditions 27 such as anaphylaxis, [28][29][30] chronic spontaneous urticaria (CSU), [31][32][33] immediate and late cutaneous reactions, 34 and rhinitis.…”

“…PAF induces IL‐6 production 15–17 and then IL‐6 stimulates production of PAF 18,19 . PAF has also been implicated in activation of the brain‐specific macrophages, microglia, 20 as well as in cancer 21,22 …”