Handbook of clinical neurology, Journal Year: 2023, Volume and Issue: unknown, P. 3 - 20
Published: Jan. 1, 2023
Language: Английский
Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 23(2), P. 115 - 128
Published: Dec. 14, 2021
Language: Английский
Citations
160
Journal of Neural Transmission, Journal Year: 2023, Volume and Issue: 130(6), P. 827 - 838
Published: May 11, 2023
The heterogeneity of Parkinson's disease (PD), i.e. the various clinical phenotypes, pathological findings, genetic predispositions and probably also implicated pathophysiological pathways pose a major challenge for future research projects therapeutic trail design. We outline several concepts, mechanisms, including presumed roles α-synuclein misfolding aggregation, Lewy bodies, oxidative stress, iron melanin, deficient autophagy processes, insulin incretin signaling, T-cell autoimmunity, gut-brain axis evidence that microbial (viral) agents may induce molecular hallmarks neurodegeneration. hypothesis is discussed, whether PD might indeed be triggered by exogenous (infectious) in susceptible individuals upon entry via olfactory bulb (brain first) or gut (body-first), which would support idea mechanisms change over time. unresolved have contributed to failure past trials, attempted slow course PD. thus conclude patients need personalized approaches tailored specific phenomenological etiologic subtypes disease.
Language: Английский
Citations
67
Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 19(6), P. 333 - 345
Published: May 4, 2023
Language: Английский
Citations
42
Progress in Neurobiology, Journal Year: 2021, Volume and Issue: 210, P. 102211 - 102211
Published: Dec. 24, 2021
Language: Английский
Citations
58
The Lancet Neurology, Journal Year: 2021, Volume and Issue: 20(10), P. 868 - 876
Published: Sept. 15, 2021
Language: Английский
Citations
57
Brain, Journal Year: 2021, Volume and Issue: 145(5), P. 1743 - 1756
Published: Dec. 13, 2021
Parkinson's disease is a progressive neurodegenerative disorder characterized by the intracellular accumulation of insoluble alpha-synuclein aggregates into Lewy bodies and neurites. Increasing evidence indicates that progression results from spread pathologic through neuronal networks. However, exact mechanisms underlying propagation abnormal proteins in brain are only partially understood. The objective this study was first to describe long-term spatiotemporal distributions Lewy-related pathology mice injected with preformed fibrils then recreate these patterns using computational model simulates silico alpha-synuclein. In study, 87 2-3-month-old non-transgenic were generate comprehensive post-mortem dataset representing hyperphosphorylated alpha-synuclein, an established marker pathology, across 426 regions Allen Mouse Brain Atlas. either caudoputamen, nucleus accumbens or hippocampus, followed over 24 months quantified at seven intermediate time points. observed each point high-resolution compared those generated Susceptible-Infected-Removed (SIR) model, agent-based for every region taking simultaneously account effect regional connectivity Snca gene expression. Our histopathological findings showed differentially targeted seeding pathological resulted unique most permissive pathology. We found SIR recreated injection site. Null models both expression had significant influence on fit. sum, our demonstrates combination normal concentration connectomics contributes making more vulnerable process, providing support prion-like propose rich related will help test new hypotheses regarding may alter brain.
Language: Английский
Citations
48
Journal of Neural Transmission, Journal Year: 2022, Volume and Issue: 129(9), P. 1201 - 1217
Published: April 15, 2022
Abstract The clinical presentation of Parkinson’s disease (PD) is both complex and heterogeneous, its precise classification often requires an intensive work-up. differential diagnosis, assessment progression, evaluation therapeutic responses, or identification PD subtypes frequently remains uncertain from a point view. Various tissue- fluid-based biomarkers are currently being investigated to improve the description PD. From clinician's perspective, signatures blood that relatively easy obtain would have great potential for use in practice if they fulfill necessary requirements as biomarker. In this review article, we summarize knowledge on blood-based present researcher’s clinician’s perspective recent developments future applications.
Language: Английский
Citations
37
Movement Disorders, Journal Year: 2021, Volume and Issue: 36(9), P. 2094 - 2103
Published: May 3, 2021
ABSTRACT Background Prodromal Parkinson's disease of skin, genitourinary, and gastrointestinal systems offers a unique window for understanding early pathogenesis developing modifying treatments. However, prior studies are limited by incomplete timing information, small sample size, lack adjustment known confounders. Verifying prodromal identifying new disorders in these accessible organs is critically important given their broad use. Objective We aimed to measure onset gastrointestinal, skin large, nationwide clinically characterized cohort 1.5 million participants. Methods Patients with (n = 303,693) were identified using diagnostic codes the medical records database United States Veterans Affairs healthcare system compared 4:1 matched controls. Disorder prevalence estimated times assessed 20 years preceding diagnosis. Results The earliest significantly increased gastroesophageal reflux, sexual dysfunction, esophageal dyskinesia at 17, 16, 15 before Estimated each disorder occurred 5.5 ± 3.4 first measured increase. smell/taste, upper tract, dysfunction 20.9, 20.6, 20.1 Onset constipation urinary notably longer 7 9 sleep patients. Dermatophytosis prostatic hypertrophy as high disorders. Conclusions Gastrointestinal, manifest decades diagnosis disease, reiterating potential sites testing pathogenesis.
Language: Английский
Citations
34
Journal of Parkinson s Disease, Journal Year: 2024, Volume and Issue: 14(s2), P. S353 - S365
Published: Feb. 6, 2024
Assessing imaging biomarker in the prodromal and early phases of Parkinson’s disease (PD) is great importance to ensure an safe diagnosis. In last decades, modalities advanced are now able assess many different aspects neurodegeneration PD. MRI sequences can measure iron content or neuromelanin. Apart from SPECT with Ioflupane, more specific PET tracers degeneration dopaminergic system available. Furthermore, metabolic patterns be used anticipate a phenoconversion PD manifest this regard, it worth mentioning that inflammation will gain significance. Molecular neurotransmitters like serotonin, noradrenaline acetylcholine shed light on non-motor symptoms. Outside brain, molecular heart gut PD-related autonomous nervous system. Moreover, optical coherence tomography noninvasively detect retinal fibers as potential review, we describe these state-of-the-art point out how far techniques future pave way towards biomarker-based staging
Language: Английский
Citations
5
Movement Disorders, Journal Year: 2022, Volume and Issue: 37(10), P. 2066 - 2074
Published: Aug. 9, 2022
Abstract Background α‐Synuclein pathology is associated with neuronal degeneration in Parkinson's disease (PD) and considered to sequentially spread across the brain (Braak stages). According a new hypothesis of distinct α‐synuclein spreading directions based on initial site pathology, “brain‐first” subtype would be more asymmetric cerebral nigrostriatal than “body‐first” subtype. Objective Here, we tested if proposed markers brain‐first PD (ie, higher dopamine transporter [DaT] asymmetry; absence rapid eye movement sleep behavior disorder [RBD]) are greater or reduction gray matter volume (GMV) comparison body‐first PD. Methods Data 255 de novo patients 110 healthy controls (HCs) were retrieved from Progression Markers Initiative. Structural magnetic resonance images preprocessed, GMVs their hemispherical asymmetry obtained for each neuropathologically defined Braak stages. Group correlation comparisons performed assess differences GMV between subtypes. Results demonstrated significantly smaller bilateral compared HCs, pattern denoting stage‐dependent disease‐related atrophy. However, degree putaminal DaT was not reduced asymmetry. Furthermore, RBD‐negative RBD‐positive did demonstrate significant difference Conclusions Our findings suggest that putative do present diverging atrophy patterns. Although certainly disproving brain‐first/body‐first hypothesis, this study fails provide evidence support it. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC behalf International Parkinson Disorder Society
Language: Английский
Citations
22