Mitochondrial DNA in CSF distinguishes LRRK2 from idiopathic Parkinson's disease.
Mitochondrial 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(G2019S) mutation carriers with Parkinson's disease, 26 asymptomatic LRRK2(G2019S) 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(G2019S) mutation carriers with Parkinson's disease exhibit a high concentration of mitochondrial DNA in CSF compared with asymptomatic LRRK2(G2019S) 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.
Neurobiology Unit, Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (CSIC), Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
Petar
P
Podlesniy
Neurology Service, Parkinson's Disease and Movement Disorders Unit, Institut Clínic de Neurociències, Hospital Clínic de Barcelona, University of Barcelona, Spain.
Dolores
D
Vilas
BioLegend, Inc., Dedham, MA, USA.
Peggy
P
Taylor
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Leslie M
LM
Shaw
Neurology Service, Parkinson's Disease and Movement Disorders Unit, Institut Clínic de Neurociències, Hospital Clínic de Barcelona, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
Eduard
E
Tolosa
Neurobiology Unit, Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (CSIC), Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain. Electronic address: ramon.trullas@iibb.csic.es.
Ramon
R
Trullas
D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010300:Parkinson Disease / Q000134:cerebrospinal fluid*; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid / Q000235:genetics
D004272:DNA, Mitochondrial; D051844:alpha-Synuclein; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
Digital PCR; LRRK2; Mitochondrial DNA; Parkinson's disease