Striatal dopamine depletion drives disease progression and network topology aberrations specifically by impairing left primary motor cortex network DOI Creative Commons
Jun Liu, Zhichun Chen, Guanglu Li

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 31, 2023

Abstract The understanding of pathophysiological mechanisms underlying symptom severity and brain network aberrations in Parkinson’s disease (PD) can offer objective, theoretically supported targets to develop novel interventions prevent the onset progression motor non-motor symptoms. objective current study is explore how stratal dopamine depletion, a pathogenic driver PD, shapes networks. PD participants (n = 141) undergoing functional magnetic resonance imaging from Progression Markers Initiative (PPMI) database were investigated. Based on quartiles striatal binding ratio (SBR) striatum, patients divided into Q1 group (SBR level rank: 0%~25%), Q2-3 25%~75%), Q4 75%~100%). associations between depletion clinical manifestations or networks characterized by integrative analysis, multiple linear regression mediation analysis. exhibited worsening symptoms compared group. Additionally, both structural topology significantly differ Specifically, connectivity left primary cortex (M1) was much lower group, which mediated topological disruptions network. Importantly, impaired M1 subnetwork aberrant effects These data demonstrate that specifically impairs disturb precipitate symptoms, supporting realistic neuromodulation target for PD.

Language: Английский

Temporal trends in the prevalence of Parkinson's disease from 1980 to 2023: a systematic review and meta-analysis DOI Creative Commons

Jinqiao Zhu,

Yusha Cui,

Junjiao Zhang

et al.

The Lancet Healthy Longevity, Journal Year: 2024, Volume and Issue: 5(7), P. e464 - e479

Published: June 27, 2024

Parkinson's disease is the second most common neurodegenerative disorder, exhibiting an upward trend in prevalence. We aimed to investigate prevalence of disease, temporal trends between 1980 and 2023, variations by location, age, sex, survey period, sociodemographic index (SDI), human development (HDI), study characteristics (sample size, diagnostic criteria, data source).

Language: Английский

Citations

58
Global, regional, national epidemiology and trends of Parkinson’s disease from 1990 to 2021: findings from the Global Burden of Disease Study 2021 DOI Creative Commons

Yuanrong Luo,

Lichun Qiao, Miaoqian Li

et al.

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 10, 2025

In light of the escalating global incidence Parkinson's disease and dearth therapeutic interventions that can alter disease's course, there exists an urgent necessity to comprehensively elucidate quantify burden. This study analyzed incidence, prevalence, disability-adjusted life years (DALYs) at global, regional, national levels based on Global Burden Disease Study 2021. Bayesian age-period cohort (BAPC) analysis was used predict burden in from 2022 2035. 2021, 11.77 million people worldwide had disease. Age-standardized rates DALYs increased 15.63/100,000, 138.63/100,000, 89.59/100,000. The were higher males than females, showed increase then a slight decrease with age. highest East Asia. BAPC projection all metrics by 2035 except for age-standardized rates. has risen over past 32 years, is need focus key populations, as well improve health policies prevent treat

Language: Английский

Citations

7
Age and sex differentially shape brain networks in Parkinson's disease DOI Creative Commons
Zhichun Chen, Bin Wu, Guanglu Li

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 29(7), P. 1907 - 1922

Published: March 8, 2023

Abstract Aims Age and sex are important individual factors modifying the clinical symptoms of patients with Parkinson's disease (PD). Our goal is to evaluate effects age on brain networks manifestations PD patients. Methods participants ( n = 198) receiving functional magnetic resonance imaging from Progression Markers Initiative database were investigated. Participants classified into lower quartile group (age rank: 0%~25%), interquartile 26%~75%), upper 76%~100%) according their quartiles examine how shapes network topology. The differences topological properties between male female also Results in exhibited disrupted topology white matter impaired integrity fibers compared group. In contrast, preferentially shaped small‐world gray covariance network. Differential metrics mediated cognitive function Conclusion have diverse structural patients, highlighting roles management PD.

Language: Английский

Citations

24
Modeling the neuroimmune system in Alzheimer’s and Parkinson’s diseases DOI Creative Commons
Wendy Balestri, Ruchi Sharma, Victor Allisson da Silva

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Jan. 23, 2024

Abstract Parkinson’s disease (PD) and Alzheimer’s (AD) are neurodegenerative disorders caused by the interaction of genetic, environmental, familial factors. These diseases have distinct pathologies symptoms that linked to specific cell populations in brain. Notably, immune system has been implicated both diseases, with a particular focus on dysfunction microglia, brain’s resident cells, contributing neuronal loss exacerbating symptoms. Researchers use models neuroimmune gain deeper understanding physiological biological aspects these how they progress. Several vitro vivo models, including 2D cultures animal utilized. Recently, advancements made optimizing existing developing 3D organ-on-a-chip systems, holding tremendous promise accurately mimicking intricate intracellular environment. As result, represent crucial breakthrough transformation current treatments for PD AD offering potential conducting long-term disease-based modeling therapeutic testing, reducing reliance significantly improving viability compared conventional models. The application research marks prosperous step forward, providing more realistic representation complex interactions within system. Ultimately, refined aim aid quest combat mitigate impact debilitating patients their families.

Language: Английский

Citations

16
The mechanism of cuproptosis in Parkinson’s disease DOI
Min Huang,

Yong Zhang,

Xuehong Liu

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 95, P. 102214 - 102214

Published: Feb. 2, 2024

Language: Английский

Citations

14
Age-associated changes in innate and adaptive immunity: role of the gut microbiota DOI Creative Commons
Haoyu Gao, Eugenie Nepovimová, Vojtěch Adam

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 16, 2024

Aging is generally regarded as an irreversible process, and its intricate relationship with the immune system has garnered significant attention due to profound implications for health well-being of aging population. As people age, a multitude alterations occur within system, affecting both innate adaptive immunity. In realm immunity, brings about changes in number function various cells, including neutrophils, monocytes, macrophages. Additionally, certain pathways, like cGAS-STING, become activated. These can potentially result telomere damage, disruption cytokine signaling, impaired recognition pathogens. The too, undergoes myriad age advances. include shifts number, frequency, subtype, T cells B cells. Furthermore, human gut microbiota dynamic part process. Notably, interplay between highlights gut’s role modulating responses maintaining homeostasis. centenarians exhibits characteristics akin those found young individuals, setting it apart from observed typical elderly individuals. This review delves into current understanding how impacts suggests potential strategies reversing through interventions factors.

Language: Английский

Citations

5
Unraveling sex differences in Parkinson's disease through explainable machine learning DOI Creative Commons

Gianfrancesco Angelini,

Antonio Malvaso,

Aurelia Schirripa

et al.

Journal of the Neurological Sciences, Journal Year: 2024, Volume and Issue: 462, P. 123091 - 123091

Published: June 12, 2024

Sex differences affect Parkinson's disease (PD) development and manifestation. Yet, current PD identification treatments underuse these distinctions. Sex-focused literature often prioritizes prevalence rates over feature importance analysis. However, underlying aspects could make a significant for predicting PD, despite its score. Interactions between features require consideration, as do distinctions scoring disparities actual importance. For instance, higher score in males certain doesn't necessarily mean it's less important characterizing females. This article proposes an explainable Machine Learning (ML) model to elucidate factors, emphasizing the of features. insight be critical personalized medicine, suggesting need tailor data collection analysis The identifies sex-specific aiding outcomes "Healthy" or "Pathological". It adopts system-level approach, integrating heterogeneous - clinical, imaging, genetics, demographics study new biomarkers diagnosis. ML approach aids non-ML experts understanding decisions, fostering trust facilitating interpretation complex outcomes, thus enhancing usability translational research. muscle rigidity, autonomic cognitive assessments, family history key contributors diagnosis, with sex noted. genetic variant SNCA-rs356181 may more males. Interaction reveals greater occurrence interplay among compared These offer insights into pathophysiology guide diagnostic therapeutic approaches.

Language: Английский

Citations

2
Parkinson’s disease-associated genetic variants synergistically shape brain networks DOI Open Access
Zhichun Chen, Bin Wu, Guanglu Li

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Dec. 27, 2022

Summary Background Over 90 genetic variants have been found to be associated with Parkinson’s disease (PD) in genome-wide association studies, however, the neural mechanisms of previously identified risk PD were largely unexplored. The objective this study was evaluate associations between PD-associated and brain gene expressions, clinical features, networks. Methods patients (n = 198) receiving magnetic resonance imaging examinations from Progression Markers Initiative (PPMI) database included analysis. effects assayed PPMI on manifestations networks systematically evaluated. Findings Most 14 failed reach stringent p -value threshold 0.00026 (0.05/14 variables x variants). Shared distinct network metrics significantly shaped by variants. Small-worldness properties at global level nodal caudate putamen basal ganglia preferentially modified. gray matter covariance mediated OGFOD2/CCDC62 rs11060180 motor assessments patients. Interpretation Our findings support that both shared are modified severity Future studies encouraged explore underlying pathogenesis. Funding This work supported grants National Key Research Development Program (2016YFC1306505) Natural Science Foundation China (81471287, 81071024, 81171202).

Language: Английский

Citations

11
Novel Insights Into the Causal Effects and Shared Genetics Between Body Fat and Parkinson Disease DOI Creative Commons
Qian Zhao, Dongming Liu, Ancha Baranova

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(11)

Published: Nov. 1, 2024

ABSTRACT Aims Existing observational studies examining the effect of body fat on risk Parkinson disease (PD) have yielded inconsistent results. We aimed to investigate this causal relationship at genetic level. Methods employed two‐sample Mendelian randomization (TSMR) effects PD, with multiple sex‐specific measures being involved. performed Bayesian colocalization analysis and cross‐trait meta‐analysis reveal pleiotropic genomic loci shared between mass index (BMI) PD. Finally, we used MAGMA tool perform tissue enrichment genome‐wide association study hits BMI. Results TSMR suggests that except waist circumference, higher fatness are associated a decreased including BMI (OR: 0.83), percentage 0.69), 0.77), hip circumference 0.83). The observed were slightly more pronounced in females than males. Colocalization highlighted two colocalized regions (chromosome 3p25.3 chromosome 17p12) by PD pointed some genes as possible players, SRGAP3 , MTMR14 ADORA2B . Cross‐trait successfully identified 10 novel loci, involving TOX3 MAP4K4 Tissue showed BMI‐associated variants enriched brain tissues. Conclusions found nonabdominal exerts robust protective against Our variation providing new clues for understanding

Language: Английский

Citations

2
BIN3rs2280104 T allele is associated with excessive daytime sleepiness and altered network topology in Parkinson’s disease DOI Open Access
Zhichun Chen, Bin Wu, Guanglu Li

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 18, 2023

Abstract Background Excessive daytime sleepiness (EDS) is one of the most common non-motor symptoms in Parkinson’s disease (PD). Previous studies showed that PD patients with EDS exhibited more severe motor and symptoms. Our recent revealed BIN3 rs2280104 was negatively associated scores Epworth Sleepiness Scale (ESS) patients. The objective this study to examine whether shapes brain networks network metrics mediate effects on EDS. Methods (n = 144) receiving functional magnetic resonance imaging Progression Markers Initiative (PPMI) database were investigated. clinical manifestations graphical structural compared among different genotype groups rs2280104. mediation analysis used explore causal associations between modified by Results ESS T allele Additionally, significantly shaped nodal Cp left superior temporal pole degree centrality calcarine scores, however, only mediated Conclusions To summarize, topology Future required identify molecular mechanisms underlying

Language: Английский

Citations

4