Brain mitochondrial impairment in early‐onset Parkinson's disease with or without PINK1 mutation

• Published in: Movement disorders Vol. 35; no. 3; pp. 504 - 507
• Main Authors: Rango, Mario, Dossi, Gabriele, Squarcina, Letizia, Bonifati, Cristiana
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.03.2020; Wiley Subscription Services, Inc
• Subjects: Adenosine triphosphate; Age of Onset; Brain - diagnostic imaging; brain mitochondrial functioning; brain pH; early‐onset Parkinson's disease (EOPD); Humans; Intracellular; Magnetic resonance spectroscopy; Mitochondria; Mitochondria - genetics; Movement disorders; Mutation; Mutation - genetics; Neurodegenerative diseases; Parkinson Disease - complications; Parkinson Disease - genetics; Parkinson's disease; pH effects; Phosphocreatine; phosphorus magnetic resonance spectroscopy (MRS); PINK1 gene mutation; Protein Kinases - genetics; PTEN-induced putative kinase; brain pH; brain mitochondrial functioning; phosphorus magnetic resonance spectroscopy (MRS); early-onset Parkinson's disease (EOPD); PINK1 gene mutation
• ISSN: 0885-3185; 1531-8257; 1531-8257
• DOI: 10.1002/mds.27946

Background PINK1 mutations are likely to affect mitochondrial function. The objective of this study was to study brain mitochondrial function in patients with early‐onset Parkinson's disease, with or without PINK1 mutations. Methods We investigated brain intracellular pH, mitochondrial activity, and energetics with functional magnetic resonance spectroscopy in patients with early‐onset Parkinson's disease with PINK1 mutations (n = 10), early‐onset Parkinson's disease without PINK1 mutations (n = 10), and healthy sex‐ and age‐matched subjects (n = 20). We measured peak areas of phosphocreatine and beta adenosine triphosphate. Results The EOPD‐ group had normal PCr + βATP contents at rest (P = NS) and under activation (P = NS), but reduced contents during recovery (P < 0.001). The EOPD+ group had abnormal PCr + βATP contents at rest (P < 0.001) and during activation (P < 0.001); during recovery, the contents only partially recovered (P < 0.001). Brain intracellular pH alterations were more severe with EOPD+ than with EOPD−. Conclusions Brain mitochondrial impairments were similar in early‐onset Parkinson's disease without PINK1 mutations and late‐onset Parkinson's disease. However, mitochondrial impairments were more severe in early‐onset Parkinson's disease with PINK1 mutations. © 2020 International Parkinson and Movement Disorder Society