Liquid biopsy shows differences in cfDNA fragmentation pattern between AD patients and controls: Biomarkers (non‐neuroimaging) / plasma/serum/urine biomarkers. (7th December 2020)

• Record Type: Journal Article
• Authors: Santamaria, Blanca Acha; Luquin, Idoia Blanco; Corroza, Jon; Miguel, Mikel San; Roldan, Miren; Zueco, Sara; Beiras, Itsaso Elizalde; Cabello, Carolina; Agudo, Maria Ángeles Garde; Jericó, Ivonne; Erro, Elena; Mendioroz, Maite
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 4
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.039748
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: In the field of precision medicine, liquid biopsy has been developed as a non‐invasive blood test to isolate circulating cell‐free DNA (cfDNA). Although liquid biopsy has gained much attention in oncology as a diagnostic tool, the role of liquid biopsy to aid diagnosis in neurodegenerative diseases remains unclear. Here, we investigated characteristics of plasma cfDNA in AD patients and controls. Method: Plasma cfDNA was isolated from 2 mL of plasma by using QIAmp Circulating Nucleic Acid Kit (QIAGEN) in a set of 95 subjects (43 Probable AD patients based on the NIA‐AA criteria and 52 controls). Fragment Analyzer system (Agilent formerly Advanced Analytical) was used to (1) check cfDNA purity, (2) measure concentration and (3) assess the fragmentation pattern including cfDNA length and concentration of the "classical" three cfDNA peaks. Statistical significance for intergroup differences was evaluated by Mann‐Whitney test with a significance level of 0.05. Result: The distribution of age and gender was similar between AD patients and controls. No genomic contamination was identified in cfDNA samples. Global plasma concentration of cfDNA was similar in both groups [median (IQR) 17.8 (31) in AD vs. 13.4 (10) in controls, p‐value=0.129]. However, differences were found in the concentration of the first cfDNA peak (size 166 bp) [0.019 (0.025) in AD vs. 0.033 (0.031) in controls; p‐value< 0.05] and in the concentration of the third cfDNA peak (size 534 bp) [0.099 (0.079) in AD vs. 0.193 (0.196) in controls; p‐value< 0.05]. No significant differences in cfDNA fragment length were detected between AD patients and controls. Conclusion: This exploratory study provides evidence of significant differences in the fragmentation pattern of cfDNA in AD patients compared to controls. These results suggest that liquid biopsy is a diagnostic tool worthy to be explored in larger AD cohorts.