Mitochondrial DNA differentiates Alzheimer's disease from Creutzfeldt-Jakob disease

Alzheimers Dement. 2016 May;12(5):546-55. doi: 10.1016/j.jalz.2015.12.011. Epub 2016 Jan 21.


Introduction: Low content of cell-free mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) is a biomarker of early stage Alzheimer's disease (AD), but whether mtDNA is altered in a rapid neurodegenerative dementia such as Creutzfeldt-Jakob disease is unknown.

Methods: CSF mtDNA was measured using digital polymerase chain reaction (dPCR) in two independent cohorts comprising a total of 112 patients diagnosed with sporadic Creutzfeldt-Jakob disease (sCJD), probable AD, or non-Alzheimer's type dementia.

Results: Patients with AD exhibit low mtDNA content in CSF compared with patients diagnosed with sCJD or with non-Alzheimer's type dementias. The CSF concentration of mtDNA does not correlate with Aβ, t-tau, p-tau, and 14-3-3 protein levels in CSF.

Discussion: Low-CSF mtDNA is not a consequence of brain damage and allows the differential diagnosis of AD from sCJD and other dementias. These results support the hypothesis that mtDNA in CSF is a pathophysiological biomarker of AD.

Keywords: Alzheimer's disease; Biomarker; Cerebrospinal fluid; Creutzfeldt-Jakob disease; Digital PCR; Mitochondrial DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / diagnosis*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid
  • Creutzfeldt-Jakob Syndrome / diagnosis*
  • DNA, Mitochondrial / cerebrospinal fluid*
  • Diagnosis, Differential*
  • Humans
  • tau Proteins / cerebrospinal fluid


  • Amyloid beta-Peptides
  • Biomarkers
  • DNA, Mitochondrial
  • tau Proteins

Supplementary concepts

  • Creutzfeldt-Jakob Disease, Sporadic