Cerebrospinal fluid mitochondrial DNA in the Alzheimer's disease continuum

Low levels of cell-free mitochondrial DNA (mtDNA) in the cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) patients have been identified and proposed as a novel biomarker for the disease. The lack of validation studies of previous results prompted us to replicate this finding in a comprehensive...

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Detalles Bibliográficos
Autores: Cervera Carles, Laura, Alcolea, Daniel, Estanga Alustiza, Ainara, Ecay Torres, Mirian, Izagirre Otaegi, Andrea, Clerigué, Montserrat, García Sebastián, Maite, Villanua Bernues, Jorge Alberto, Escalas, Claudia, Blesa, Rafael, Martínez-Lage Alvarez, Pablo, Lleó, Alberto, Fortea, Juan, Clarimón, Jordi
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/72300
Acceso en línea:http://hdl.handle.net/10810/72300
Access Level:acceso abierto
Palabra clave:mitochondrial DNA
Alzheimer’s disease continuum
cerebrospinal fluid
genetic biomarkers
droplet digital PCR
Descripción
Sumario:Low levels of cell-free mitochondrial DNA (mtDNA) in the cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) patients have been identified and proposed as a novel biomarker for the disease. The lack of validation studies of previous results prompted us to replicate this finding in a comprehensive series of patients and controls. We applied droplet digital polymerase chain reaction in CSF specimens from 124 patients representing the AD spectrum and 140 neurologically healthy controls. The following pre- analytical and analytical parameters were evaluated: the effect of freeze-thaw cycles on mtDNA, the linearity of mtDNA load across serial dilutions, and the mtDNA levels in the diagnostic groups. We found a wide range of mtDNA copies, which resulted in a high degree of overlap between groups. Although the AD group presented significantly higher mtDNA counts, the receiver-operating characteristic analysis disclosed an area under the curve of 0.715 to distinguish AD patients from controls. MtDNA was highly stable with low analytical variability. In conclusion, mtDNA levels in CSF show a high interindividual variability, with great overlap within phenotypes and presents low sensitivity for AD