RGS2 and SIRT1 Link Renin Angiotensin Aldosterone System to Alzheimer’s Disease

Abstract The discovery of early biomarkers for Alzheimer’s disease (AD) is required for early diagnosis and personalized preventive therapy. In an innovative approach, we have used genome-wide transcriptomic profiling of lymphoblastoid cell lines (LCLs) from healthy individuals and identified genes that predict sensitivity to Aβ. RGS2 (regulator of G-protein signaling 2) had lower expression in healthy individuals’ LCLs exhibiting higher Aβ sensitivity. Interestingly, RGS2 showed lower expression in AD LCLs compared to healthy controls. Moreover, SIRT1 (Sirtuin 1) was downregulated in AD LCLs. Thus, LCLs transcriptomics identified RGS2 , a key regulator of G protein coupled receptors and neuronal plasticity, as a novel AD biomarker. RGS2 and SIRT1 expression levels were positively correlated and both have been implicated as neuroprotective and involved in the renin-angiotensin-aldosterone system. Individual LCLs may thus serve, as surrogate for brain cells, and may point to altered transcriptomic profiles that could be implicated in AD pathology.