Circulating Cell Free DNA and DNA Double-Strand Breakage in Alzheimer's Disease

Overview

Journal J Alzheimers Dis Rep

Publisher IOS Press

Date 2024 May 15

PMID 38746625

Authors

Michelle Nguyen

Colby Wood

Andres Rios

Zach Salter

P Hemachandra Reddy

Affiliations

Soon will be listed here.

Abstract

Alzheimer's disease (AD) is an age-related neurodegenerative disease that is characterized by memory loss and multiple cognitive impairments. AD is pathologically characterized by age-dependent accumulation of amyloid-β protein and the phosphorylation of tau protein in the brains of patients with AD. Clinically, manifestations of AD include cognitive decline, dementia, alterations of high-order brain functions, and movement disorders. Double-stranded DNA breaks are a lethal form of DNA damage and are typically repaired via non-homologous end joining and homologous recombination. However, in AD brain, repair mechanism is disrupted, leading to a cascade of events, cognitive dysfunction, organ failure and reduced lifespan. Increased circulating cell-free DNA in the blood, cerebrospinal fluid, and urine in patients with AD, can be used as early detectable biomarkers for AD. The purpose of our article is to explore the potential uses of cell-free DNA and double-stranded DNA breaks as prognostic markers for AD and examine the recent research on the application of these markers in studies.

Citing Articles

The Potential of cfDNA as Biomarker: Opportunities and Challenges for Neurodegenerative Diseases.

Aydin S, Ozdemir S, Adiguzel A J Mol Neurosci. 2025; 75(1):34.

PMID: 40080233 PMC: 11906534. DOI: 10.1007/s12031-025-02317-8.

Considering Biomarkers of Neurodegeneration in Alzheimer's Disease: The Potential of Circulating Cell-Free DNA in Precision Neurology.

Pollard C, Saito E, Burns J, Hill J, Jenkins T J Pers Med. 2024; 14(11).

PMID: 39590596 PMC: 11595805. DOI: 10.3390/jpm14111104.

References

Rao K . Mechanisms of disease: DNA repair defects and neurological disease. Nat Clin Pract Neurol. 2007; 3(3):162-72. DOI: 10.1038/ncpneuro0448. View

Lopez O, DeKosky S . Clinical symptoms in Alzheimer's disease. Handb Clin Neurol. 2008; 89:207-16. DOI: 10.1016/S0072-9752(07)01219-5. View

Pollard C, Aston K, Emery B, Hill J, Jenkins T . Detection of neuron-derived cfDNA in blood plasma: a new diagnostic approach for neurodegenerative conditions. Front Neurol. 2023; 14:1272960. PMC: 10643874. DOI: 10.3389/fneur.2023.1272960. View

Luo H, Wei W, Ye Z, Zheng J, Xu R . Liquid Biopsy of Methylation Biomarkers in Cell-Free DNA. Trends Mol Med. 2021; 27(5):482-500. DOI: 10.1016/j.molmed.2020.12.011. View

Tug S, Helmig S, Deichmann E, Schmeier-Jurchott A, Wagner E, Zimmermann T . Exercise-induced increases in cell free DNA in human plasma originate predominantly from cells of the haematopoietic lineage. Exerc Immunol Rev. 2015; 21:164-73. View

Shen X, Chen J, Li J, Kofler J, Herrup K . Neurons in Vulnerable Regions of the Alzheimer's Disease Brain Display Reduced ATM Signaling. eNeuro. 2016; 3(1). PMC: 4770009. DOI: 10.1523/ENEURO.0124-15.2016. View

Kanungo J . DNA-dependent protein kinase and DNA repair: relevance to Alzheimer's disease. Alzheimers Res Ther. 2013; 5(2):13. PMC: 3706827. DOI: 10.1186/alzrt167. View

Fernandez-Lazaro D, Hernandez J, Garcia A, Cordova Martinez A, Mielgo-Ayuso J, Cruz-Hernandez J . Liquid Biopsy as Novel Tool in Precision Medicine: Origins, Properties, Identification and Clinical Perspective of Cancer's Biomarkers. Diagnostics (Basel). 2020; 10(4). PMC: 7235853. DOI: 10.3390/diagnostics10040215. View

Welch G, Boix C, Schmauch E, Davila-Velderrain J, Victor M, Dileep V . Neurons burdened by DNA double-strand breaks incite microglia activation through antiviral-like signaling in neurodegeneration. Sci Adv. 2022; 8(39):eabo4662. PMC: 9519048. DOI: 10.1126/sciadv.abo4662. View

10.

Kapaki E, Vakrakou A, Boufidou F . Novel CSF Biomarkers Tracking Autoimmune Inflammatory and Neurodegenerative Aspects of CNS Diseases. Diagnostics (Basel). 2023; 13(1). PMC: 9818715. DOI: 10.3390/diagnostics13010073. View

11.

Vogel H, Lim D, Karsenty G, Finegold M, Hasty P . Deletion of Ku86 causes early onset of senescence in mice. Proc Natl Acad Sci U S A. 1999; 96(19):10770-5. PMC: 17958. DOI: 10.1073/pnas.96.19.10770. View

12.

Jylhava J, Kotipelto T, Raitala A, Jylha M, Hervonen A, Hurme M . Aging is associated with quantitative and qualitative changes in circulating cell-free DNA: the Vitality 90+ study. Mech Ageing Dev. 2010; 132(1-2):20-6. DOI: 10.1016/j.mad.2010.11.001. View

13.

Thadathil N, Delotterie D, Xiao J, Hori R, McDonald M, Khan M . DNA Double-Strand Break Accumulation in Alzheimer's Disease: Evidence from Experimental Models and Postmortem Human Brains. Mol Neurobiol. 2020; 58(1):118-131. DOI: 10.1007/s12035-020-02109-8. View

14.

OConnell G, Chantler P, Barr T . High Interspecimen Variability in Nucleic Acid Extraction Efficiency Necessitates the Use of Spike-In Control for Accurate qPCR-based Measurement of Plasma Cell-Free DNA Levels. Lab Med. 2017; 48(4):332-338. PMC: 5907903. DOI: 10.1093/labmed/lmx043. View

15.

Kovacs G . Molecular pathology of neurodegenerative diseases: principles and practice. J Clin Pathol. 2019; 72(11):725-735. DOI: 10.1136/jclinpath-2019-205952. View

16.

Zhu L, Wang D, Cui K, Liu D, Zhu L . Emerging Perspectives on DNA Double-strand Breaks in Neurodegenerative Diseases. Curr Neuropharmacol. 2019; 17(12):1146-1157. PMC: 7057204. DOI: 10.2174/1570159X17666190726115623. View

17.

Su J, Deng G, Cotman C . Neuronal DNA damage precedes tangle formation and is associated with up-regulation of nitrotyrosine in Alzheimer's disease brain. Brain Res. 1998; 774(1-2):193-9. DOI: 10.1016/s0006-8993(97)81703-9. View

18.

Briguglio S, Cambria C, Albizzati E, Marcello E, Provenzano G, Frasca A . New Views of the DNA Repair Protein Ataxia-Telangiectasia Mutated in Central Neurons: Contribution in Synaptic Dysfunctions of Neurodevelopmental and Neurodegenerative Diseases. Cells. 2023; 12(17). PMC: 10486624. DOI: 10.3390/cells12172181. View

19.

Nakanishi A, Minami A, Kitagishi Y, Ogura Y, Matsuda S . BRCA1 and p53 tumor suppressor molecules in Alzheimer's disease. Int J Mol Sci. 2015; 16(2):2879-92. PMC: 4346871. DOI: 10.3390/ijms16022879. View

20.

Hao X, Luo H, Krawczyk M, Wei W, Wang W, Wang J . DNA methylation markers for diagnosis and prognosis of common cancers. Proc Natl Acad Sci U S A. 2017; 114(28):7414-7419. PMC: 5514741. DOI: 10.1073/pnas.1703577114. View