Objective: To identify markers of resistance to developing Parkinson disease (PD) among mutation carriers (+), we carried out metabolomic profiling in individuals with PD and unaffected controls (UC), with and without the mutation.
Methods: Plasma from 368 patients with PD and UC in the LRRK2 Cohort Consortium (LCC), comprising 118 +/PD+, 115 +/UC, 70 -/PD+, and 65 /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 and PD status, using analysis of covariance models adjusted by age, study site cohort, and sex, with value corrections for multiple comparisons.
Results: Plasma caffeine concentration was lower in patients with PD vs UC ( < 0.001), more so among + carriers (by 76%) than among - participants (by 31%), with significant interaction between and PD status ( = 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 PD+ compared to UC with significant interaction effect with the mutation ( < 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 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 mutation carriers.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836665 | PMC |
| http://dx.doi.org/10.1212/WNL.0000000000010863 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Basal forebrain global functional connectivity is preserved in asymptomatic presenilin-1 E280A mutation carriers: Results from the Colombia cohort.
J Prev Alzheimers Dis
February 2025
Department of Psychosomatic Medicine, University Medicine Rostock, Rostock, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Greifswald, Rostock, Germany.
Background: Imaging studies showed early atrophy of the cholinergic basal forebrain in prodromal sporadic Alzheimer's disease and reduced posterior basal forebrain functional connectivity in amyloid positive individuals with subjective cognitive decline. Similar investigations in familial cases of Alzheimer's disease are still lacking.
Objectives: To test whether presenilin-1 E280A mutation carriers have reduced basal forebrain functional connectivity and whether this is linked to amyloid pathology.
Breast cancer outcomes after skin- and nipple-sparing mastectomy in BRCA pathogenic mutation carriers versus non-BRCA carriers.
Radiother Oncol
January 2025
School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Radiation Unit, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel; GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands. Electronic address:
Unlabelled: Our previous study on BRCA breast cancer carriers disclosed a high local recurrence (LR) rate in patients who underwent skin sparing (SSM) or nipple sparing mastectomy (NSM) without postoperative radiation therapy (RT), compared to breast conservation surgery or mastectomy with RT. The current study compares the LR rates in BRCA versus non BRCA carriers after SSM/NSM in relation the receipt of RT.
Methods: The study was approved by the institutional ethics committee.
Amyotrophic lateral sclerosis caused by FUS mutations: advances with broad implications.
Lancet Neurol
February 2025
Department of Neurosciences, and Leuven Brain Institute, University of Leuven, Leuven, Belgium; Laboratory of Neurobiology, Center for Brain & Disease Research, VIB, Leuven, Belgium. Electronic address:
Autosomal dominant mutations in the gene encoding the DNA and RNA binding protein FUS are a cause of amyotrophic lateral sclerosis (ALS), and about 0·3-0·9% of patients with ALS are FUS mutation carriers. FUS-mutation-associated ALS (FUS-ALS) is characterised by early onset and rapid progression, compared with other forms of ALS. However, different pathogenic mutations in FUS can result in markedly different age at symptom onset and rate of disease progression.
View Article and Find Full Text PDFBiallelic mutations in CDC20 cause female infertility due to oocyte maturation abnormality.
Gynecol Endocrinol
December 2025
Department of Reproductive Medicine, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.
Oocyte maturation arrest (OMA) may occur at different stages, including the germinal vesicle (GV), metaphase I (MI), and metaphase II (MII). A total maturation arrest of human oocytes is rarely observed during fertilization (IVF). We have identified a case of infertile female for whom all oocytes fail to mature and are arrested at MI.
View Article and Find Full Text PDFNeurobehavioral Outcomes Relate to Activation Ratio in Female Carriers of Fragile X Syndrome Full Mutation: Two Pediatric Case Studies.
Int J Mol Sci
January 2025
Department of Women's and Children's Health, University of Padova, 35128 Padova, Italy.
Fragile X syndrome (FXS) is a genetic neurodevelopmental disorder that causes a range of developmental problems including cognitive and behavioral impairment and learning disabilities. FXS is caused by full mutations (FM) of the gene expansions to over 200 repeats, with hypermethylation of the cytosine-guanine-guanine (CGG) tandem repeated region in its promoter, resulting in transcriptional silencing and loss of gene function. Female carriers of FM are typically less impaired than males.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!