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Title: | Cerebrospinal Fluid Mitochondrial DNA in Rapid and Slow Progressive Forms of Alzheimer's Disease |
Author: | Podlesniy, Petar Llorens Torres, Franc Puigros, Margalida Serra, Nuria Sepúlveda Falla, Diego Schmidt, Christian Hermann, Peter Zerr, Inga Trullas, Ramon |
Keywords: | ADN mitocondrial Malaltia d'Alzheimer Líquid cefalorraquidi Mitochondrial DNA Alzheimer's disease Cerebrospinal fluid |
Issue Date: | 1-Sep-2020 |
Publisher: | MDPI |
Abstract: | Alzheimer's type dementia (AD) exhibits clinical heterogeneity, as well as differences in disease progression, as a subset of patients with a clinical diagnosis of AD progresses more rapidly (rpAD) than the typical AD of slow progression (spAD). Previous findings indicate that low cerebrospinal fluid (CSF) content of cell-free mitochondrial DNA (cf-mtDNA) precedes clinical signs of AD. We have now investigated the relationship between cf-mtDNA and other biomarkers of AD to determine whether a particular biomarker profile underlies the different rates of AD progression. We measured the content of cf-mtDNA, beta-amyloid peptide 1-42 (A beta), total tau protein (t-tau) and phosphorylated tau (p-tau) in the CSF from a cohort of 95 subjects consisting of 49 controls with a neurologic disorder without dementia, 30 patients with a clinical diagnosis of spAD and 16 patients with rpAD. We found that 37% of controls met at least one AD biomarker criteria, while 53% and 44% of subjects with spAD and rpAD, respectively, did not fulfill the two core AD biomarker criteria: high t-tau and low A beta in CSF. In the whole cohort, patients with spAD, but not with rpAD, showed a statistically significant 44% decrease of cf-mtDNA in CSF compared to control. When the cohort included only subjects selected by A beta and t-tau biomarker criteria, the spAD group showed a larger decrease of cf-mtDNA (69%), whereas in the rpAD group cf-mtDNA levels remained unaltered. In the whole cohort, the CSF levels of cf-mtDNA correlated positively with A beta and negatively with p-tau. Moreover, the ratio between cf-mtDNA and p-tau increased the sensitivity and specificity of spAD diagnosis up to 93% and 94%, respectively, in the biomarker-selected cohort. These results show that the content of cf-mtDNA in CSF correlates with the earliest pathological markers of the disease, A beta and p-tau, but not with the marker of neuronal damage t-tau. Moreover, these findings confirm that low CSF content of cf-mtDNA is a biomarker for the early detection of AD and support the hypothesis that low cf-mtDNA, together with low A beta and high p-tau, constitute a distinctive CSF biomarker profile that differentiates spAD from other neurological disorders. |
Note: | Reproducció del document publicat a: https://doi.org/10.3390/ijms21176298 |
It is part of: | International Journal of Molecular Sciences, 2020, vol. 21, num. 17 |
URI: | http://hdl.handle.net/2445/173417 |
Related resource: | https://doi.org/10.3390/ijms21176298 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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