An RNA biomarker panel for the diagnosis of Alzheimer’s disease from whole blood

Alzheimer’s Disease (AD) diagnosis remains primarily clinical, relying on patient history, cognitive tests, and sometimes brain imaging. Emerging approaches include advanced neuroimaging techniques and the use of protein biomarkers in cerebrospinal fluid and plasma. However, these methods have limitations such as high costs and the need for specialized infrastructures. In contrast, analysis of RNA expression in blood samples could be achieved with a high degree of sensitivity and accuracy in point of care settings, providing an ideal platform for a timely and accurate AD diagnosis. Peripheral blood samples from 50 AD patients and 50 healthy subjects were analyzed utilizing a whole transcriptome RNA sequencing approach to determine differences in the expression of i) mRNAs, ii) lncRNAs, iii) miRNAs, iv) circRNAs and v) alternatively spliced mRNA isoforms. Multiple parallel analysis pipelines were utilized to identify four differentially expressed transcripts to form an AD biomarker panel. Expression levels in each AD patient were compared to those in healthy subjects to obtain an AD predictive score (ADps) with a positive predictive value of over 90% and a specificity of over 95%. The four RNA biomarkers can reliably identify AD patients using a minimal amount of peripheral blood and has the potential to be developed into a minimally invasive, cost-effective and reliable tool for early AD diagnosis.