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A metabolic profile of polyamines in parkinson disease: A promising biomarker
Author(s) -
Saiki Shinji,
Sasazawa Yukiko,
Fujimaki Motoki,
Kamagata Koji,
Kaga Naoko,
Taka Hikari,
Li Yuanzhe,
Souma Sanae,
Hatano Taku,
Imamichi Yoko,
Furuya Norihiko,
Mori Akio,
Oji Yutaka,
Ueno ShinIchi,
Nojiri Shuko,
Miura Yoshiki,
Ueno Takashi,
Funayama Manabu,
Aoki Shigeki,
Hattori Nobutaka
Publication year - 2019
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25516
Subject(s) - biomarker , parkinson's disease , disease , medicine , neuroscience , chemistry , biology , biochemistry
Objective Aging is the highest risk factor for Parkinson disease (PD). Under physiological conditions, spermidine and spermine experimentally enhance longevity via autophagy induction. Accordingly, we evaluated the ability of each polyamine metabolite to act as an age‐related, diagnostic, and severity‐associated PD biomarker. Methods Comprehensive metabolome analysis of plasma was performed in Cohort A (controls, n = 45; PD, n = 145), followed by analysis of 7 polyamine metabolites in Cohort B (controls, n = 49; PD, n = 186; progressive supranuclear palsy, n = 19; Alzheimer disease, n = 23). Furthermore, 20 patients with PD who were successively examined within Cohort B were studied using diffusion tensor imaging (DTI). Association of each polyamine metabolite with disease severity was assessed according to Hoehn and Yahr stage (H&Y) and Unified Parkinson's Disease Rating Scale motor section (UPDRS‐III). Additionally, the autophagy induction ability of each polyamine metabolite was examined in vitro in various cell lines. Results In Cohort A, N 8‐acetylspermidine and N ‐acetylputrescine levels were significantly and mildly elevated in PD, respectively. In Cohort B, spermine levels and spermine/spermidine ratio were significantly reduced in PD, concomitant with hyperacetylation. Furthermore, N 1, N 8‐diacetylspermidine levels had the highest diagnostic value, and correlated with H&Y, UPDRS‐III, and axonal degeneration quantified by DTI. The spermine/spermidine ratio in controls declined with age, but was consistently suppressed in PD. Among polyamine metabolites, spermine was the strongest autophagy inducer, especially in SH‐SY5Y cells. No significant genetic variations in 5 genes encoding enzymes associated with spermine/spermidine metabolism were detected compared with controls. Interpretation Spermine synthesis and N 1, N 8‐diacetylspermidine may respectively be useful diagnostic and severity‐associated biomarkers for PD. ANN NEUROL 2019;86:251–263