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Title

Mitochondrial DNA in CSF distinguishes LRRK2 from idiopathic Parkinson's disease

AuthorsPodlesniy, Petar ; Vilas, Dolores; Taylor, Peggy; Shaw, Leslie M.; Tolosa, Eduardo; Trullas, Ramón
KeywordsParkinson's disease
Digital PCR
Mitochondrial DNA
LRRK2
Issue DateOct-2016
PublisherElsevier
CitationNeurobiology of Disease 94: 10-17 (2016)
AbstractMitochondrial DNA regulates mitochondrial function which is altered in both idiopathic and familial forms of Parkinson's disease. To investigate whether these two disease forms exhibit an altered regulation of mitochondrial DNA we measured cell free mitochondrial DNA content in cerebrospinal fluid (CSF) from idiopathic and LRRK2-related Parkinson's disease patients. The concentration of mitochondrial DNA was measured using a digital droplet polymerase chain reaction technique in a total of 98 CSF samples from a cohort of subjects including: 20 LRRK2 mutation carriers with Parkinson's disease, 26 asymptomatic LRRK2 mutation carriers, 31 patients with idiopathic Parkinson's disease and 21 first-degree relatives of LRRK2 Parkinson's disease patients without the mutation. Here we report that LRRK2 mutation carriers with Parkinson's disease exhibit a high concentration of mitochondrial DNA in CSF compared with asymptomatic LRRK2 mutation carriers and with idiopathic Parkinson's disease patients. In addition, idiopathic, but not LRRK2 Parkinson's disease is associated with low CSF concentration of α-synuclein. These results show that high mitochondrial DNA content in CSF distinguishes idiopathic from LRRK2-related Parkinson's disease suggesting that different biochemical pathways underlie neurodegeneration in these two disorders.
Publisher version (URL)https://doi.org/10.1016/j.nbd.2016.05.019
URIhttp://hdl.handle.net/10261/148759
DOI10.1016/j.nbd.2016.05.019
Identifiersdoi: 10.1016/j.nbd.2016.05.019
issn: 1095-953X
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