Davin Lee^a,1, Yoon Ha Choi^b,1, Jinsoo Seo^a, Jong Kyoung Kim^b,*, Sung Bae Lee^a,*

^aDepartment of Brain & Cognitive Sciences, DGIST, Daegu, Republic of Korea
^bDepartment of New Biology, DGIST, Daegu, Republic of Korea

¹These authors contributed equally.

^*Corresponding authors

Treatment options for many neurodegenerative diseases are limited due to the lack of early diagnostic procedures that allow timely delivery of therapeutic agents to affected neurons prior to cell death. While notable advances have been made in neurodegenerative disease biomarkers, whether or not the biomarkers discovered to date are useful for early diagnosis remains an open question. Additionally, the reliability of these biomarkers has been disappointing, due in part to the large dissimilarities between the tissues traditionally used to source biomarkers and primarily diseased neurons. In this article, we review the potential viability of atypical epigenetic and/or consequent transcriptional alterations (ETAs) as biomarkers of early-stage neurodegenerative disease, and present our perspectives on the discovery and practical use of such biomarkers in patient-derived neural samples using single-cell level analyses, thereby greatly enhancing the reliability of biomarker application.

Keyword : Neurodegenerative diseases; iPSC; Organoid; Single-cell sequencing; Epigenetic alteration; Transcriptional alteration