English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/89279
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:


Low cerebrospinal fluid concentration of mitochondrial DNA in preclinical Alzheimer disease

Other TitlesLow CSF concentration of mitochondrial DNA in preclinical Alzheimer’s disease
AuthorsPodlesniy, Petar ; Figueiro-Silva, Joana ; Serra, Nuria ; Trullas, Ramón
Issue DateNov-2013
CitationAnnals of Neurology 74(5): 655-668 (2013)
Abstract[Objective]: To identify a novel biochemical marker that precedes clinical symptoms in Alzheimer disease (AD). [Methods]: Using quantitative polymerase chain reaction techniques, we measured circulating cell-free mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) from study participants, selected from a cohort of 282 subjects, who were classified according to their concentrations of amyloid β1–42, total tau, and phosphorylated tau and by the presence or absence of dementia, into asymptomatic subjects at risk of AD, symptomatic patients diagnosed with sporadic AD, presymptomatic subjects carrying pathogenic PSEN1 mutations, and patients diagnosed with frontotemporal lobar degeneration (FTLD). We performed equivalent studies in a separate validation cohort of sporadic AD and FTLD patients. In addition, we measured mtDNA copy number in cultured cortical neurons from mutant amyloid precursor protein/presenilin1 (APP/PS1) transgenic mice. [Results]: Asymptomatic patients at risk of AD and symptomatic AD patients, but not FTLD patients, exhibit a significant decrease in circulating cell-free mtDNA in the CSF. These observations were confirmed in the validation cohort. In addition, presymptomatic subjects carrying pathogenic PSEN1 gene mutations show low mtDNA content in CSF before the appearance of AD-related biomarkers in CSF. Moreover, mtDNA content in CSF discriminates with high sensitivity and specificity AD patients from either controls or patients with FTLD. Furthermore, cultured cortical neurons from APP/PS1 transgenic mice have fewer mtDNA copies before the appearance of altered synaptic markers. [Interpretation]: Low content of mtDNA in CSF may be a novel biomarker for the early detection of preclinical AD. These findings support the hypothesis that mtDNA depletion is a characteristic pathophysiological factor of neurodegeneration in AD.
DescriptionTítulo diferente en el postprint: Low CSF concentration of mitochondrial DNA in preclinical Alzheimer’s disease
Publisher version (URL)http://dx.doi.org/10.1002/ana.23955
Appears in Collections:(IIBB) Artículos
Files in This Item:
File Description SizeFormat 
Podlesniy-ANeurology-2013-v74-p655.pdf547,92 kBAdobe PDFThumbnail
Show full item record
Review this work

Related articles:

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.