Format

Send to

Choose Destination
Neurobiol Aging. 2017 May;53:192.e1-192.e4. doi: 10.1016/j.neurobiolaging.2016.12.009. Epub 2016 Dec 22.

Cerebrospinal fluid mitochondrial DNA in the Alzheimer's disease continuum.

Author information

1
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.
2
Department of Neurology, Fundación CITA-Alzhéimer Fundazioa, San Sebastián, Spain.
3
Department of Neurology, Fundación CITA-Alzhéimer Fundazioa, San Sebastián, Spain; Donostia Unit, Osatek SA, Donostia University Hospital, San Sebastián, Spain.
4
Memory Unit, Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
5
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.
6
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.
7
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.

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.

KEYWORDS:

Alzheimer's disease continuum; Cerebrospinal fluid; Droplet digital PCR; Genetic biomarkers; Mitochondrial DNA

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center