Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson's disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here, we identify as a new gene implicated in PD and childhood neurodegeneration.
View Article and Find Full Text PDFNPJ Parkinsons Dis
January 2024
Although many rare variants have been reportedly associated with Parkinson's disease (PD), many have not been replicated or have failed to replicate. Here, we conduct a large-scale replication of rare PD variants. We assessed a total of 27,590 PD cases, 6701 PD proxies, and 3,106,080 controls from three data sets: 23andMe, Inc.
View Article and Find Full Text PDFSerotonin (5-hydroxytryptamine) acts as a widespread neuromodulator in the nervous system of vertebrates and invertebrates. In insects, it promotes feeding, enhances olfactory sensitivity, modulates aggressive behavior, and, in the central complex of Drosophila, serves a role in sleep homeostasis. In addition to a role in sleep-wake regulation, the central complex has a prominent role in spatial orientation, goal-directed locomotion, and navigation vector memory.
View Article and Find Full Text PDFObjective: Although many rare variants have been reportedly associated with Parkinson's disease (PD), many have not been replicated or have failed to replicate. Here, we conduct a large-scale replication of rare PD variants.
Methods: We assessed a total of 27,590 PD cases, 6,701 PD proxies, and 3,106,080 controls from three data sets: 23andMe, Inc.
Background: Neuropathological studies, based on small samples, suggest that symptoms of Parkinson's disease (PD) emerge when dopamine/nigrostriatal loss is around 50-80%. Functional neuroimaging can be applied in larger numbers during life, which allows analysis of the extent of dopamine loss more directly.
Objective: To quantify dopamine transporter (DaT) activity by neuroimaging in early PD.
The Foundational Data Initiative for Parkinson Disease (FOUNDIN-PD) is an international collaboration producing fundamental resources for Parkinson disease (PD). FOUNDIN-PD generated a multi-layered molecular dataset in a cohort of induced pluripotent stem cell (iPSC) lines differentiated to dopaminergic (DA) neurons, a major affected cell type in PD. The lines were derived from the Parkinson's Progression Markers Initiative study, which included participants with PD carrying monogenic PD variants, variants with intermediate effects, and variants identified by genome-wide association studies and unaffected individuals.
View Article and Find Full Text PDFBackground: Biallelic pathogenic variants in GBA1 are the cause of Gaucher disease (GD) type 1 (GD1), a lysosomal storage disorder resulting from deficient glucocerebrosidase. Heterozygous GBA1 variants are also a common genetic risk factor for Parkinson's disease (PD). GD manifests with considerable clinical heterogeneity and is also associated with an increased risk for PD.
View Article and Find Full Text PDFEndocannabinoid (eCB), 2-arachidonoyl-glycerol (2-AG), the most abundant eCB in the brain, regulates diverse neural functions. Here we linked multiple homozygous loss-of-function mutations in 2-AG synthase diacylglycerol lipase β (DAGLB) to an early onset autosomal recessive Parkinsonism. DAGLB is the main 2-AG synthase in human and mouse substantia nigra (SN) dopaminergic neurons (DANs).
View Article and Find Full Text PDFObjectives: Hyposmia is a common feature of Parkinson's disease (PD), yet there is no standard method to define it. A comparison of four published methods was performed to explore and highlight differences.
Materials And Methods: Olfactory testing was performed in 2097 cases of early PD in two prospective studies.
Background: A good response to levodopa is a key feature of Parkinson's disease (PD), and a poor response suggests an alternative diagnosis, but the extent of variation in the levodopa response in definite PD is not well defined.
Literature Review: A systematic review of articles reporting pathologically confirmed PD and levodopa responsiveness from 1971 to 2018 was performed using the medical subheadings "postmortem," "Parkinson's disease," "levodopa," and "l-dopa" in PubMed, Embase, and Latin American and Caribbean Health Sciences Literature (LILACS) databases.
Cases: A total of 12 articles described 445 PD cases: 61.
Background: L-dopa responsiveness in Parkinson's disease (PD) varies, but the clinical correlates and significance of this are ill-defined.
Methods: Patients were assessed before and after their usual morning L-dopa dose, using the MDS Unified PD Rating Scale Part 3 (MDS UPDRS 3), and rated as definite responders (≥24.5% improvement) or limited responders (<24.