Cerebrospinal fluid mitochondrial DNA in the Alzheimer's disease continuum
Por:
Cervera-Carles, L, Alcolea, D, Estanga, A, Ecay-Torres, M, Izagirre, A, Clerigue, M, Garcia-Sebastian, M, Villanua, J, Escalas, C, Blesa, R, Martinez-Lage, P, Lleo, A, Fortea, J, Clarimon, J
Publicada:
1 may 2017
Resumen:
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. (C) 2016 Elsevier Inc. All rights reserved.
Filiaciones:
Cervera-Carles, L:
Univ Autonoma Barcelona, Hosp Santa Crue & St Pau, IIB St Pau, Dept Neurol,Memory Unit, Barcelona, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Alcolea, D:
Univ Autonoma Barcelona, Hosp Santa Crue & St Pau, IIB St Pau, Dept Neurol,Memory Unit, Barcelona, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Estanga, A:
Fdn CITA, Alzheimer Fundazioa, Dept Neurol, San Sebastian, Spain
Ecay-Torres, M:
Fdn CITA, Alzheimer Fundazioa, Dept Neurol, San Sebastian, Spain
Izagirre, A:
Fdn CITA, Alzheimer Fundazioa, Dept Neurol, San Sebastian, Spain
Clerigue, M:
Fdn CITA, Alzheimer Fundazioa, Dept Neurol, San Sebastian, Spain
Garcia-Sebastian, M:
Fdn CITA, Alzheimer Fundazioa, Dept Neurol, San Sebastian, Spain
Villanua, J:
Fdn CITA, Alzheimer Fundazioa, Dept Neurol, San Sebastian, Spain
Donostia Univ Hosp, Osatek SA, Donostia Unit, San Sebastian, Spain
Escalas, C:
Univ Autonoma Barcelona, Hosp Santa Crue & St Pau, IIB St Pau, Dept Neurol,Memory Unit, Barcelona, Spain
Blesa, R:
Univ Autonoma Barcelona, Hosp Santa Crue & St Pau, IIB St Pau, Dept Neurol,Memory Unit, Barcelona, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Martinez-Lage, P:
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Fdn CITA, Alzheimer Fundazioa, Dept Neurol, San Sebastian, Spain
Lleo, A:
Univ Autonoma Barcelona, Hosp Santa Crue & St Pau, IIB St Pau, Dept Neurol,Memory Unit, Barcelona, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Fortea, J:
Univ Autonoma Barcelona, Hosp Santa Crue & St Pau, IIB St Pau, Dept Neurol,Memory Unit, Barcelona, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Clarimon, J:
Univ Autonoma Barcelona, Hosp Santa Crue & St Pau, IIB St Pau, Dept Neurol,Memory Unit, Barcelona, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
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