Role of extrachromosomal circular DNA in aging and neurodegeneration / Eye-Tracking as a Diagnostic Tool for Mild Cognitive Impairment in Clinical Settings: a Validation Study

The aging process is a major risk factor for neurodegeneration and central nervous system (CNS) disorders, with associated causal pathways including the accumulation of genomic damage and defects in programmed genome modifications. One by-product of altered genome plasticity is extrachromosomal circular DNA (eccDNA). Although eccDNA is ubiquitous in the eukaryotic genome, its role in health and disease, aging and neurodegeneration is poorly understood. Recent data have revealed an intriguing complexity of mechanisms by which eccDNA influences the copy number, expression and transcription of pathogenicity genes hosted on circular DNA and throughout the linear genome. The present study demonstrates how a new computational approach that links eccDNAs to individual genes to form Produced per Gene Circles (PpGCs) complements length- or size-based analysis of eccDNA marker detection in CNS tissue. It discusses eccDNA as an unconventional episomal genome regulator that offers a novel perspective for the diagnostic evaluation of age-related CNS disorders.

Detecting MCI patients at an early stage could significantly contribute to the development of more effective interventions aimed at delaying the onset of other pathologies. Nevertheless, existing analytical and diagnostic clinical approaches are time-consuming and often dependent on the subjectivity of the clinician when diagnosing a patient. Eye-Tracking (ET) is a low-cost, effective, and non-invasive technique that, despite its wide use in research, has not yet been fully embraced in clinical settings. ET measures the eye movements of a participant while they attend to different stimuli, and numerous studies have demonstrated a strong relation between these movements and cognitive status. However, to the best of our knowledge, only a handful of studies have attempted to create a dedicated ET battery to detect MCI in patients. In this study, we aim to (1) present a comprehensive battery test designed to assess the cognitive capabilities of multiple participants, (2) quantify a wide range of ET measures, and (3) use these measures to seek a relation with certain psychological scores. This represents an initial step towards developing a tool that can aid in diagnosing MCI patients, with significant implications for the primary healthcare system.