title: Cerebrospinal fluid mitochondrial DNA in the Alzheimer's disease continuum.
abstract: 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 preanalytical 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.
authors.affiliation: Memory Unit, Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Cervera-Carles
authors.affiliation: Memory Unit, Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Alcolea
authors.affiliation: Department of Neurology, Fundación CITA-Alzhéimer Fundazioa, San Sebastián, Spain.
authors.forename: Ainara
authors.initials: A
authors.lastname: Estanga
authors.affiliation: Department of Neurology, Fundación CITA-Alzhéimer Fundazioa, San Sebastián, Spain.
authors.forename: Mirian
authors.initials: M
authors.lastname: Ecay-Torres
authors.affiliation: Department of Neurology, Fundación CITA-Alzhéimer Fundazioa, San Sebastián, Spain.
authors.forename: Andrea
authors.initials: A
authors.lastname: Izagirre
authors.affiliation: Department of Neurology, Fundación CITA-Alzhéimer Fundazioa, San Sebastián, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Clerigué
authors.affiliation: Department of Neurology, Fundación CITA-Alzhéimer Fundazioa, San Sebastián, Spain.
authors.forename: Maite
authors.initials: M
authors.lastname: García-Sebastián
authors.affiliation: Department of Neurology, Fundación CITA-Alzhéimer Fundazioa, San Sebastián, Spain; Donostia Unit, Osatek SA, Donostia University Hospital, San Sebastián, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Villanúa
authors.affiliation: Memory Unit, Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Clàudia
authors.initials: C
authors.lastname: Escalas
authors.affiliation: Memory Unit, Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Blesa
authors.affiliation: Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain; Department of Neurology, Fundación CITA-Alzhéimer Fundazioa, San Sebastián, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Martínez-Lage
authors.affiliation: Memory Unit, Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Lleó
authors.affiliation: Memory Unit, Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: jfortea@santpau.cat.
authors.forename: Juan
authors.initials: J
authors.lastname: Fortea
authors.affiliation: Memory Unit, Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: jclarimon@santpau.cat.
authors.forename: Jordi
authors.initials: J
authors.lastname: Clarimón
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D004272:DNA, Mitochondrial / Q000134:cerebrospinal fluid*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D012372:ROC Curve
chemical_list: D015415:Biomarkers; D004272:DNA, Mitochondrial; D005819:Genetic Markers
keywords: Alzheimer's disease continuum; Cerebrospinal fluid; Droplet digital PCR; Genetic biomarkers; Mitochondrial DNA