Decreased long-chain acylcarnitines from insufficient β-oxidation as potential early diagnostic markers for Parkinson’s disease

Abstract Increasing evidence shows that metabolic abnormalities in body fluids are distinguishing features of the pathophysiology of Parkinson’s disease. However, a non-invasive approach has not been established in the earliest or pre-symptomatic phases. Here, we report comprehensive double-cohort a...

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Autores principales: Shinji Saiki, Taku Hatano, Motoki Fujimaki, Kei-Ichi Ishikawa, Akio Mori, Yutaka Oji, Ayami Okuzumi, Takeshi Fukuhara, Takahiro Koinuma, Yoko Imamichi, Miho Nagumo, Norihiko Furuya, Shuko Nojiri, Taku Amo, Kazuo Yamashiro, Nobutaka Hattori
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/39cf9e83253748d8b72eb80e81610158
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Sumario:Abstract Increasing evidence shows that metabolic abnormalities in body fluids are distinguishing features of the pathophysiology of Parkinson’s disease. However, a non-invasive approach has not been established in the earliest or pre-symptomatic phases. Here, we report comprehensive double-cohort analyses of the metabolome using capillary electrophoresis/liquid chromatography mass-spectrometry. The plasma analyses identified 18 Parkinson’s disease-specific metabolites and revealed decreased levels of seven long-chain acylcarnitines in two Parkinson’s disease cohorts (n = 109, 145) compared with controls (n = 32, 45), respectively. Furthermore, statistically significant decreases in five long-chain acylcarnitines were detected in Hoehn and Yahr stage I. Likewise, decreased levels of acylcarnitine(16:0), a decreased ratio of acylcarnitine(16:0) to fatty acid(16:0), and an increased index of carnitine palmitoyltransferase 1 were identified in Hoehn and Yahr stage I of both cohorts, suggesting of initial β-oxidation suppression. Receiver operating characteristic curves produced using 12–14 long-chain acylcarnitines provided a large area of under the curve, high specificity and moderate sensitivity for diagnosing Parkinson’s disease. Our data demonstrate that a primary decrement of mitochondrial β-oxidation and that 12–14 long-chain acylcarnitines decreases would be promising diagnostic biomarkers for Parkinson’s disease.