Association of caffeine and related analytes with resistance to Parkinson disease among LRRK2 mutation carriers: A metabolomic study
Crotty GF, Maciuca R, Macklin EA, Wang J, Montalban M, Davis SS, Alkabsh JI, Bakshi R, Chen X, Ascherio A, Astarita G, Huntwork-Rodriguez S, Schwarzschild MA
Neurology · 51 citas
Etiquetas de revisión
Vínculos de autores con la industriaDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
Cómo se estudió
- Diseño
- Estudio de cohortes (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiación independiente
- Organización sin fines de lucro
- Michael J. Fox Foundation for Parkinson's Research
- Organización sin fines de lucro
- Farmer Family Foundation
- Gobierno
- National Institutes of Health
- Gobierno
- National Institute of Neurological Disorders and Stroke
- Gobierno
- NINDS NIH HHS
- Autores
- Al menos un autor declara un vínculo económico con la industria
- Subvenciones
- National Institute of Neurological Disorders and Stroke (R01NS102735); National Institute of Neurological Disorders and Stroke (R21 NS090246); National Institute of Neurological Disorders and Stroke (R01NS110879); National Institutes of Health (R01NS110879)
Según 5 financiadores declarados y la declaración de financiación del texto completo.
Publicación
- Publicado
- 2020-10-01 · Neurology · vol. 95 · número 24 · págs. e3428–e3437
- Editorial
- Lippincott Williams & Wilkins
- Citado
- 58 citas · más que el 93% de estudios similares · 2.8× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 37 trabajos
- Acceso
- Acceso abierto (revista híbrida) · CC-BY-NC-ND
- Áreas de investigación
- Parkinson's Disease Mechanisms and Treatments · Ginkgo biloba and Cashew Applications · Biochemical Analysis and Sensing Techniques
- Palabras clave
- LRRK2, Internal medicine, Medicine, Cohort, Caffeine, Paraxanthine, Gastroenterology, Parkinson's disease, Chemistry, Disease
- MeSH
- humans, parkinson disease, alkaloids, xanthines, caffeine, theophylline, neuroprotective agents, chromatography, liquid, cohort studies, heterozygote, aged, middle aged, female, male, mass spectrometry, metabolomics, leucine-rich repeat serine-threonine protein kinase-2
13 autores
- Grace F. Crotty🇺🇸Harvard University; Massachusetts General Hospital; Denali Therapeutics (United States)
- Romeo D. Maciuca🇺🇸Harvard University; Massachusetts General Hospital; Denali Therapeutics (United States)
- Eric A. Macklin🇺🇸Harvard University; Massachusetts General Hospital; Denali Therapeutics (United States)
- Junhua Wang🇺🇸Harvard University; Massachusetts General Hospital; Denali Therapeutics (United States)
- Manuel Montalban🇺🇸Harvard University; Massachusetts General Hospital; Denali Therapeutics (United States)
- Sonnet S. Davis🇺🇸Harvard University; Massachusetts General Hospital; Denali Therapeutics (United States)
- Jamal I. Alkabsh🇺🇸Harvard University; Massachusetts General Hospital; Denali Therapeutics (United States)
- Rachit Bakshi🇺🇸Harvard University; Massachusetts General Hospital; Denali Therapeutics (United States)
- Xiqun Chen🇺🇸Harvard University; Massachusetts General Hospital; Denali Therapeutics (United States)
- Alberto Ascherio🇺🇸Harvard University; Massachusetts General Hospital; Denali Therapeutics (United States)
- Giuseppe Astarita🇺🇸Harvard University; Massachusetts General Hospital; Denali Therapeutics (United States)
- Sarah Huntwork‐Rodriguez🇺🇸Harvard University; Massachusetts General Hospital; Denali Therapeutics (United States)
- Michael A. Schwarzschild🇺🇸Harvard University; Massachusetts General Hospital; Denali Therapeutics (United States)
Resumen
El texto original del estudio, en el idioma en que se publicó.
Objective
To identify markers of resistance to developing Parkinson disease (PD) among LRRK2 mutation carriers (LRRK2+), we carried out metabolomic profiling in individuals with PD and unaffected controls (UC), with and without the LRRK2 mutation.
Methods
Plasma from 368 patients with PD and UC in the LRRK2 Cohort Consortium (LCC), comprising 118 LRRK2+/PD+, 115 LRRK2+/UC, 70 LRRK2-/PD+, and 65 LRRK2-/UC, and CSF available from 68 of them, were analyzed by liquid chromatography with mass spectrometry. For 282 analytes quantified in plasma and CSF, we assessed differences among the 4 groups and interactions between LRRK2 and PD status, using analysis of covariance models adjusted by age, study site cohort, and sex, with p value corrections for multiple comparisons.
Results
Plasma caffeine concentration was lower in patients with PD vs UC (p LRRK2+ carriers (by 76%) than among LRRK2- participants (by 31%), with significant interaction between LRRK2 and PD status (p = 0.005). Similar results were found for caffeine metabolites (paraxanthine, theophylline, 1-methylxanthine) and a nonxanthine marker of coffee consumption (trigonelline) in plasma, and in the subset of corresponding CSF samples. Dietary caffeine was also lower in LRRK2+/PD+ compared to LRRK2+/UC with significant interaction effect with the LRRK2+ mutation (p < 0.001).
Conclusions
Metabolomic analyses of the LCC samples identified caffeine, its demethylation metabolites, and trigonelline as prominent markers of resistance to PD linked to pathogenic LRRK2 mutations, more so than to idiopathic PD. Because these analytes are known both as correlates of coffee consumption and as neuroprotectants in animal PD models, the findings may reflect their avoidance by those predisposed to develop PD or their protective effects among LRRK2 mutation carriers.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY-NC-ND).
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