Uncharacterized RNAs in Plasma of Alzheimer’s Patients Are Associated with Cognitive Impairment and Show a Potential Diagnostic Power

Abstract

Alzheimer’s disease (AD) diagnosis is actually based on clinical evaluation and brain-imaging tests, and it can often be confirmed only post-mortem. Therefore, new non-invasive molecular biomarkers are necessary to improve AD diagnosis. As circulating microRNA biomarkers have been proposed for many diseases, including AD, we aimed to identify new diagnostic non-small RNAs in AD. Whole transcriptome analysis was performed on plasma samples of five AD and five unaffected individuals (CTRL) using the Clariom D Pico Assay, followed by validation in real-time PCR on 37 AD patients and 37 CTRL. Six differentially expressed (DE) transcripts were identified: GS1-304P7.3 (upregulated), NONHSAT090268, TC0100011037, TC0400008478, TC1400008125, and UBE2V1 (downregulated). Peripheral blood mononuclear cells (PBMCs) may influence the expression of circulating RNAs and their analysis has been proposed to improve AD clinical management. Accordingly, DE transcript expression was also evaluated in PBMCs, showing no difference between AD and CTRL. ROC (receiver operating characteristic) curve analysis was performed to evaluate the diagnostic accuracy of each DE transcript and a signature including all of them. A correlation between cognitive impairment and GS1-304P7.3, NONHSAT090268, TC0100011037, and TC0400008478 was detected, suggesting a potential association between their extracellular abundance and AD clinical phenotype. Finally, this study identified six transcripts showing altered expression in the plasma of AD patients. Given the need for new, accurate blood biomarkers for AD diagnosis, these transcripts may be considered for further analyses in larger cohorts, also in combination with other biomarkers, aiming to identify specific RNA-based biomarkers to be eventually applied to clinical practice.

Serum Extracellular Vesicle-Derived circHIPK3 and circSMARCA5 Are Two Novel Diagnostic Biomarkers for Glioblastoma Multiforme

“…The diagnostic and prognostic value of these inflammatory markers in GBM has been largely described in the literature [ 69 , 70 , 71 , 72 ]. According to these data, a multivariable ROC analysis, performed by combining the expression of sEV-derived circSMARCA5 and circHIPK3 with NLR, PLR and LMR, allowed an improvement in the diagnostic value as compared to a univariable analysis: this is in accordance with other studies, confirming the strength of a diagnosis based on a multi-biomarker panel [ 73 , 74 , 75 ].…”

Clinical and Molecular Biomarkers for Diagnosis and Staging of NAFLD

“…In biological fluids, there are RNA molecules belonging to different classes, including messenger RNAs (mRNAs), long-noncoding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs). The presence of cell-free RNAs in body fluids stimulated the interest in studying these molecules as novel biomarkers of diagnosis, prognosis, monitoring and therapeutic response of several kinds of pathologies [ 75 , 76 , 77 , 78 ].…”

Leukocyte-derived ratios are associated with late-life any type dementia: a cross-sectional analysis of the Mugello study

“…The progression of these processes culminates with the imbalance between adaptive/innate immune response, CNS invasion by peripheral monocytes [10], lymphocyte proliferation [7], and hyperactivation of microglial phagocytic cells [2]. Because of the association between dementia pathogenesis and the immune system, several studies on immune cells as biological markers are emerging [11]. The recent COVID-19 pandemic has renewed the interest in leukocyte countderived indexes, which are easily available at no extra cost, and represent possible markers of inflammation with predictive value for disease outcome, not only in the elderly.…”