Serum metabolic biomarkers for synucleinopathy conversion in isolated REM sleep behavior disorder
Laguna, Ariadna (Hospital Universitari Vall d'Hebron)
Xicoy, Helena (Donders Institute for Brain)
Tolosa, Eduardo (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Serradell, Mònica (Hospital Clínic i Provincial de Barcelona)
Vilas Rolán, Dolores (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Gaig, Carles (Hospital Clínic i Provincial de Barcelona)
Fernández, Manel (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Yanes, Oscar (Universitat Rovira i Virgili)
Santamaria Cano, Joan (Hospital Clínic i Provincial de Barcelona)
Amigó, Núria (Biosfer Teslab, Reus)
Iranzo, Alex (Hospital Clínic i Provincial de Barcelona)
Vila Bover, Miquel (Institució Catalana de Recerca i Estudis Avançats)
Universitat Autònoma de Barcelona

Data:	2021
Resum:	Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal stage of Lewy-type synucleinopathies (LTS), which can present either with an initial predominant parkinsonism (Parkinson's disease (PD)) or dementia (dementia with Lewy bodies (DLB)). To provide insights into the underlying pathogenic mechanisms, the lipoprotein and protein glycosylation profile of 82 iRBD patients, collected before and/or after their conversion to an overt LTS, and 29 matched control serum samples were assessed by nuclear magnetic resonance (NMR) spectroscopy. Data were statistically analyzed to identify altered metabolites and construct predictive models. Univariant analysis detected no differences between iRBD patients with an LTS compared to controls. However, significant differences were found when the analysis distinguished between iRBD patients that manifested initially predominant parkinsonism (pre-PD) or dementia (pre-DLB). Significant differences were also found in the analysis of paired iRBD samples pre- and post-LTS diagnosis. Predictive models were built and distinguished between controls and pre-DLB patients, and between pre-DLB and pre-PD patients. This allowed a prediction of the possible future clinical outcome of iRBD patients. We provide evidence of altered lipoprotein and glycosylation profiles in subgroups of iRBD patients. Our results indicate that metabolic alterations and inflammation are involved in iRBD pathophysiology, and suggest biological differences underlying the progression of LTS in iRBD patients. Our data also indicate that profiling of serum samples by NMR may be a useful tool for identifying short-term high-risk iRBD patients for conversion to parkinsonism or dementia.
Ajuts:	Ministerio de Economía y Competitividad PI13/01897 Ministerio de Economía y Competitividad SAF2015-73997-JIN Agencia Estatal de Investigación SAF2016-77541-R
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Predictive markers ; Neurodegeneration ; Parkinson's disease
Publicat a:	NPJ Parkinson's disease, Vol. 7 (may 2021) , ISSN 2373-8057

DOI: 10.1038/s41531-021-00184-9
PMID: 33986284

8 p, 1.0 MB

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