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

• Published in: Alzheimer's & dementia Vol. 12; no. 5; pp. 546 - 555
• Main Authors: Podlesniy, Petar, Llorens, Franc, Golanska, Ewa, Sikorska, Beata, Liberski, Pawel, Zerr, Inga, Trullas, Ramon
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2016
• Subjects: Alzheimer Disease - diagnosis; Alzheimer's disease; Amyloid beta-Peptides - cerebrospinal fluid; Biomarker; Biomarkers - cerebrospinal fluid; Cerebrospinal fluid; Creutzfeldt-Jakob disease; Creutzfeldt-Jakob Syndrome - diagnosis; Diagnosis, Differential; Digital PCR; DNA, Mitochondrial - cerebrospinal fluid; Humans; Mitochondrial DNA; tau Proteins - cerebrospinal fluid; Biomarker; Mitochondrial DNA; Digital PCR; Cerebrospinal fluid; Alzheimer's disease; Creutzfeldt-Jakob disease
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1016/j.jalz.2015.12.011

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.
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.
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.
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.