This study attempted to identify a novel biochemical marker that precedes clinical symptoms of Alzheimer’s disease (AD). Using quantitative PCR techniques, the authors measured circulating cell free mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) from study participants, selected from a cohort of 282 subjects that were classified according to their concentrations of Aβ1-42, t-tau and p-tau and by the presence or absence of dementia, including asymptomatic subjects at risk of AD, symptomatic patients diagnosed with sporadic AD, pre-symptomatic subjects carrying pathogenic PSEN1 mutations and patients diagnoses with Fronto-temporal Lobar Degeneration (FTLD). They performed equivalent studies in a separate validation cohort of sporadic AD and FTLD patients. They easured mtDNA copy number in cultured cortical neurons from mutant Amyloid Precursor Protein/Presenilin1 transgenic mice. The results showed that 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. The authors conclude that the low content of mtDNA in CSF may be a novel biomarker for the early detection of preclinical AD. These findings also support the hypothesis that mtDNA depletion is a characteristic pathophysiological factor of neurodegeneration in AD. Ann Neurol. 2013 Jun. PMID: 23794434
