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Regional Brain Metabolism across the Alzheimer's Disease Continuum in Down Syndrome 唐氏综合症患者阿尔茨海默病连续体的区域脑代谢
IF 8.1 1区 医学
Annals of Neurology Pub Date : 2025-03-14 DOI: 10.1002/ana.27226
José Enrique Arriola-Infante MD, Alejandra O. Morcillo-Nieto MSc, Sara E. Zsadanyi MSc, María Franquesa-Mullerat Msc, Lídia Vaqué-Alcázar PhD, Mateus Rozalem-Aranha MD, PhD, Javier Arranz MD, Íñigo Rodríguez-Baz MD, PhD, Lucia Maure-Blesa MD, Laura Videla PhD, Isabel Barroeta MD, PhD, Laura Del Hoyo Soriano PhD, Bessy Benejam PhD, Susana Fernández MD, Aida Sanjuan-Hernández BSc, Sandra Giménez MD, PhD, Daniel Alcolea MD, PhD, Olivia Belbin PhD, Albert Flotats MD, PhD, Valle Camacho MD, PhD, Alberto Lleó MD, PhD, María Carmona-Iragui MD, PhD, Juan Fortea MD, PhD, Alexandre Bejanin PhD
{"title":"Regional Brain Metabolism across the Alzheimer's Disease Continuum in Down Syndrome","authors":"José Enrique Arriola-Infante MD,&nbsp;Alejandra O. Morcillo-Nieto MSc,&nbsp;Sara E. Zsadanyi MSc,&nbsp;María Franquesa-Mullerat Msc,&nbsp;Lídia Vaqué-Alcázar PhD,&nbsp;Mateus Rozalem-Aranha MD, PhD,&nbsp;Javier Arranz MD,&nbsp;Íñigo Rodríguez-Baz MD, PhD,&nbsp;Lucia Maure-Blesa MD,&nbsp;Laura Videla PhD,&nbsp;Isabel Barroeta MD, PhD,&nbsp;Laura Del Hoyo Soriano PhD,&nbsp;Bessy Benejam PhD,&nbsp;Susana Fernández MD,&nbsp;Aida Sanjuan-Hernández BSc,&nbsp;Sandra Giménez MD, PhD,&nbsp;Daniel Alcolea MD, PhD,&nbsp;Olivia Belbin PhD,&nbsp;Albert Flotats MD, PhD,&nbsp;Valle Camacho MD, PhD,&nbsp;Alberto Lleó MD, PhD,&nbsp;María Carmona-Iragui MD, PhD,&nbsp;Juan Fortea MD, PhD,&nbsp;Alexandre Bejanin PhD","doi":"10.1002/ana.27226","DOIUrl":"10.1002/ana.27226","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The goal was to examine the effect of sociodemographic variables, Alzheimer's disease (AD) clinical stages and pathology on brain metabolism in Down syndrome (DS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We included 71 euploid healthy controls (HC) and 105 adults with DS (67 asymptomatic, 12 prodromal, and 26 with dementia) from the Down-Alzheimer Barcelona Neuroimaging Initiative. Participants underwent [18F]fluorodeoxyglucose positron emission tomography, 3 Tmagnetic resonance imaging, and lumbar puncture to measure cerebrospinal fluid (CSF) biomarkers (ratio beween amyloid β peptide 42 and 40, phosphorylated tau 181, and neurofilament light chain [NfL]). Voxel-wise analyses in SPM12 examined the effects of age, sex, intellectual disability, Alzheimer's clinical stage, and CSF biomarkers on brain metabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In HC, brain metabolism decreased with age primarily in the frontal lobe. By contrast, a more distributed pattern of metabolic loss was observed in DS with age, predominating in temporoparietal regions. Compared to asymptomatic DS participants, those at the prodromal stage exhibited medial parietal hypometabolism, which later extended to other temporoparietal and frontal regions at the dementia stage. In asymptomatic individuals, we observed a widespread hypometabolism compared to HC, mainly in medial frontal and parietal regions. All CSF biomarkers were closely associated with hypometabolism in regions affected by the disease, with the strongest association observed for NfL in medial parietal structures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The brain metabolic decline in DS with age reflects Alzheimer's pathological processes and involves temporoparietal regions in a similar pattern to that found in other forms of AD. Hypometabolism is more tightly related to CSF NfL levels than to core AD biomarkers. ANN NEUROL 2025;98:163–173</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"98 1","pages":"163-173"},"PeriodicalIF":8.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cerebral Edema Progression and Outcomes in Large Infarct Patients Undergoing Endovascular Thrombectomy 接受血管内取栓术的大梗死患者脑水肿的进展和结局。
IF 8.1 1区 医学
Annals of Neurology Pub Date : 2025-03-11 DOI: 10.1002/ana.27235
Ximing Nie MD, Jinjie Liu MD, Bernard Yan DMedSci, Felix C. Ng MBBS, Sibo Liu MD, Yongle Wang MD, Mengxing Wang PhD, Lina Zheng MD, PhD, Zan Wang MD, Yuying Wang MD, Yuesong Pan PhD, Xiaochuan Huo MD, PhD, Zhongrong Miao MD, PhD, Stephen M. Davis MD, Liping Liu MD, PhD, for the ANGEL-ASPECT Study Group
{"title":"Cerebral Edema Progression and Outcomes in Large Infarct Patients Undergoing Endovascular Thrombectomy","authors":"Ximing Nie MD,&nbsp;Jinjie Liu MD,&nbsp;Bernard Yan DMedSci,&nbsp;Felix C. Ng MBBS,&nbsp;Sibo Liu MD,&nbsp;Yongle Wang MD,&nbsp;Mengxing Wang PhD,&nbsp;Lina Zheng MD, PhD,&nbsp;Zan Wang MD,&nbsp;Yuying Wang MD,&nbsp;Yuesong Pan PhD,&nbsp;Xiaochuan Huo MD, PhD,&nbsp;Zhongrong Miao MD, PhD,&nbsp;Stephen M. Davis MD,&nbsp;Liping Liu MD, PhD,&nbsp;for the ANGEL-ASPECT Study Group","doi":"10.1002/ana.27235","DOIUrl":"10.1002/ana.27235","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The goal was to analyze the progression of cerebral edema post-endovascular thrombectomy (EVT) in large infarcts and its association with functional outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A secondary analysis of the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core trial was conducted in patients with large ischemic cores randomized to receive either EVT or medical management (MM) alone. Patients who had follow-up imaging within 7 days post-randomization were involved. The primary outcome was midline shift (MLS). Mediation analysis was performed with EVT as the independent variable, MLS as the mediator, and modified Rankin scale scores at 90 days served as the endpoint. An exploratory analysis was conducted on the progression of net water uptake (ΔNWU).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 434 patients, median age was 66.0 years (standard deviation [SD], 9.9), with 61.3% (266) being males. EVT was associated with an early increase in MLS at 24 (±12) hours after randomization (mean [SD], 3.0 [4.2] vs 2.4 [3.6]mm; <i>p</i> = 0.03) compared with the MM group, partially mediating poorer functional outcomes post-EVT (mediation proportion, −25%; 95% CI, −46.54 to −4.10), but did not negate the overall efficacy of thrombectomy. The progression of NWU remained slower after EVT throughout 7 days, inconsistent with MLS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>In patients with large infarct cores, EVT was associated with an early increased mass effect compared with MM, potentially mediating poorer functional outcomes. Despite the evident overall benefits from thrombectomy, accurate prediction and effective anti-edema interventions for the early mass effect post-EVT may further improve outcomes. The complex relationship between NWU and cerebral edema progression warrants further investigation. ANN NEUROL 2025;98:258–269</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"98 2","pages":"258-269"},"PeriodicalIF":8.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Track Sign Distal to Internal Carotid Artery Occlusion 颈内动脉闭塞远端轨道征。
IF 8.1 1区 医学
Annals of Neurology Pub Date : 2025-03-11 DOI: 10.1002/ana.27234
Ying Yu MD, Jiabao Yang MD, Ning Ma MD
{"title":"Track Sign Distal to Internal Carotid Artery Occlusion","authors":"Ying Yu MD,&nbsp;Jiabao Yang MD,&nbsp;Ning Ma MD","doi":"10.1002/ana.27234","DOIUrl":"10.1002/ana.27234","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"98 1","pages":"183-184"},"PeriodicalIF":8.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Network Localization of Pediatric Lesion-Induced Dystonia 小儿病变性肌张力障碍的网络定位。
IF 8.1 1区 医学
Annals of Neurology Pub Date : 2025-03-10 DOI: 10.1002/ana.27224
Rose Gelineau-Morel MD, Nomazulu Dlamini MD, PhD, Joel Bruss BA, Alexander L. Cohen MD, PhD, Amanda Robertson MSc, Dimitrios Alexopoulos MS,, Christopher D. Smyser MD, Aaron D. Boes MD, PhD
{"title":"Network Localization of Pediatric Lesion-Induced Dystonia","authors":"Rose Gelineau-Morel MD,&nbsp;Nomazulu Dlamini MD, PhD,&nbsp;Joel Bruss BA,&nbsp;Alexander L. Cohen MD, PhD,&nbsp;Amanda Robertson MSc,&nbsp;Dimitrios Alexopoulos MS,,&nbsp;Christopher D. Smyser MD,&nbsp;Aaron D. Boes MD, PhD","doi":"10.1002/ana.27224","DOIUrl":"10.1002/ana.27224","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Dystonia is a movement disorder defined by involuntary muscle contractions leading to abnormal postures or twisting and repetitive movements. Classically dystonia has been thought of as a disorder of the basal ganglia, but newer results in idiopathic dystonia and lesion-induced dystonia in adults point to broader motor network dysfunction spanning the basal ganglia, cerebellum, premotor cortex, sensorimotor, and frontoparietal regions. It is unclear whether a similar network is shared between different etiologies of pediatric lesion-induced dystonia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Three cohorts of pediatric patients with lesion-induced dystonia were identified. The lesion etiologies included hypoxia, kernicterus, and stroke versus comparison subjects with acquired lesions not associated with dystonia. Multivariate lesion-symptom mapping and lesion network mapping were used to evaluate the anatomy and networks associated with dystonia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Multivariate lesion-symptom mapping showed that lesions of the putamen and globus pallidus were associated with dystonia (<i>r</i> = 0.41, <i>p</i> &lt; 0.001). Lesion network mapping using normative connectome data from healthy children demonstrated that these regional findings occurred within a common brain-wide network that involves the basal ganglia, anterior and medial cerebellum, and cortical regions that overlap the cingulo-opercular action-mode and somato-cognitive-action networks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>We interpret these findings as novel evidence for a unified dystonia brain network that involves the somato-cognitive-action network, which is implicated in the coordination of movement. Elucidation of this network gives insight into the functional origins of dystonia and provides novel targets to investigate for therapeutic intervention. ANN NEUROL 2025;98:152–162</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"98 1","pages":"152-162"},"PeriodicalIF":8.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Annals of Neurology: Volume 97, Number 4, April 2025 神经病学年鉴:第97卷,第4号,2025年4月
IF 8.1 1区 医学
Annals of Neurology Pub Date : 2025-03-08 DOI: 10.1002/ana.26979
{"title":"Annals of Neurology: Volume 97, Number 4, April 2025","authors":"","doi":"10.1002/ana.26979","DOIUrl":"https://doi.org/10.1002/ana.26979","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 4","pages":"C1"},"PeriodicalIF":8.1,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26979","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Blood DDIT4 and TRIM13 Transcript Levels Mark the Early Stages of Machado–Joseph Disease 血液DDIT4和TRIM13转录物水平标志着马查多-约瑟夫病的早期阶段。
IF 8.1 1区 医学
Annals of Neurology Pub Date : 2025-03-05 DOI: 10.1002/ana.27222
Ana F. Ferreira PhD, Mafalda Raposo PhD, Emily D. Shaw MSc, Louisa Liu, João Vasconcelos MD, Teresa Kay MD, Conceição Bettencourt PhD, Maria Luiza Saraiva-Pereira MD, PhD, Laura Bannach Jardim MD, PhD, Maria do Carmo Costa PhD, Manuela Lima PhD
{"title":"Blood DDIT4 and TRIM13 Transcript Levels Mark the Early Stages of Machado–Joseph Disease","authors":"Ana F. Ferreira PhD,&nbsp;Mafalda Raposo PhD,&nbsp;Emily D. Shaw MSc,&nbsp;Louisa Liu,&nbsp;João Vasconcelos MD,&nbsp;Teresa Kay MD,&nbsp;Conceição Bettencourt PhD,&nbsp;Maria Luiza Saraiva-Pereira MD, PhD,&nbsp;Laura Bannach Jardim MD, PhD,&nbsp;Maria do Carmo Costa PhD,&nbsp;Manuela Lima PhD","doi":"10.1002/ana.27222","DOIUrl":"10.1002/ana.27222","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>An abundance of select transcripts and proteins has been found to be dysregulated in blood samples of Machado–Joseph disease (MJD) carriers. Here, we aimed to: (1) identify blood transcriptional changes as potential biomarkers of MJD; (2) correlate levels of differentially expressed blood transcripts with MJD carriers features; and (3) evaluate whether the identified differential abundance of blood transcripts in MJD patients is preserved in MJD brains.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used unbiased RNA microarray and quantitative polymerase chain reaction to assess transcript levels in blood and brain samples, and western blot analysis to evaluate the abundance of specific proteins in brain samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We observed consistent dysregulation of <i>DDIT4</i>, <i>TRIM13</i>, and <i>P2RY13</i> transcriptional levels in the blood of MJD patients from preclinical to symptomatic stages in Azorean and Brazilian cohorts. Combined blood <i>DDIT4</i> and <i>TRIM13</i> transcriptional levels show a very high accuracy to discriminate MJD carriers from matched controls (AUC ≥0.90). Levels of <i>P2RY13</i> transcripts correlate with age at onset, and an abundance of <i>DDIT4</i> and <i>TRIM13</i> transcripts correlate with the expanded CAG repeat size in combined Azorean and Brazilian patients; and levels of <i>TRIM13</i> transcripts correlate with age at onset of early-stage Azorean patients. Moreover, the abundance of TRIM13 protein is increased in the cerebral cortex of MJD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Overall, blood <i>DDIT4</i> and <i>TRIM13</i> transcript levels are potential biomarkers of MJD. Cellular processes involving <i>DDIT4</i>, <i>TRIM13</i>, and <i>P2RY13</i> appear to be commonly dysregulated in the blood and brain of MJD patients, indicating the involvement of these genes in MJD pathogenesis. ANN NEUROL 2025;98:107–119</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"98 1","pages":"107-119"},"PeriodicalIF":8.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27222","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Purine Metabolism and Dystonia: Perspectives of a Long-Promised Relationship 嘌呤代谢和肌张力障碍:一个长期承诺的关系的观点。
IF 8.1 1区 医学
Annals of Neurology Pub Date : 2025-03-03 DOI: 10.1002/ana.27227
Ugo Sorrentino MD, Audrey G. O'Neill BSc, Justin M. Kollman PhD, Hyder A. Jinnah MD, PhD, Michael Zech MD
{"title":"Purine Metabolism and Dystonia: Perspectives of a Long-Promised Relationship","authors":"Ugo Sorrentino MD,&nbsp;Audrey G. O'Neill BSc,&nbsp;Justin M. Kollman PhD,&nbsp;Hyder A. Jinnah MD, PhD,&nbsp;Michael Zech MD","doi":"10.1002/ana.27227","DOIUrl":"10.1002/ana.27227","url":null,"abstract":"<p>Dystonia research focuses on the identification of converging biological pathways, allowing to define molecular drivers that serve as treatment targets. We summarize evidence supporting the concept that aberrations in purine metabolism intersect with dystonia pathogenesis. The recent discovery of <i>IMPDH2</i>-related dystonia introduced a gain-of-function paradigm in purinergic system defects, offering new perspectives to understand purine-pool imbalances in brain diseases. We discuss commonalities between known dystonia-linked mechanisms and mechanisms emerging from studies of purine metabolism disorders including Lesch–Nyhan disease. Together, we hypothesize that a greater appreciation of the relevance of purine perturbances in dystonia can offer fresh avenues for therapeutic intervention. ANN NEUROL 2025;97:809–825</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 5","pages":"809-825"},"PeriodicalIF":8.1,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27227","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Starry Cortex of Aβ-Related Angiitis a β相关性脉管炎的星形皮质。
IF 8.1 1区 医学
Annals of Neurology Pub Date : 2025-03-03 DOI: 10.1002/ana.27228
Shiyuan Fang MD, Nan Jiang MD, Lixin Zhou MD, Jun Ni MD
{"title":"The Starry Cortex of Aβ-Related Angiitis","authors":"Shiyuan Fang MD,&nbsp;Nan Jiang MD,&nbsp;Lixin Zhou MD,&nbsp;Jun Ni MD","doi":"10.1002/ana.27228","DOIUrl":"10.1002/ana.27228","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 6","pages":"1219-1221"},"PeriodicalIF":8.1,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Plasma Glucosylceramide Levels Are Regulated by ATP10D and Are Not Involved in Parkinson's Disease Pathogenesis 血浆葡萄糖甘油三酯水平受 ATP10D 调节,与帕金森病发病机制无关
IF 8.1 1区 医学
Annals of Neurology Pub Date : 2025-03-01 DOI: 10.1002/ana.27219
Emma N. Somerville BSc, Alva James PhD, Christian Beetz PhD, Robert Schwieger PhD, Gal Barrel PhD, Krishna K. Kandaswamy PhD, Marius I. Iurascu PhD, Peter Bauer MD, Michael Ta MS, Hirotaka Iwaki MD, PhD, Konstantin Senkevich MD, PhD, Eric Yu PhD, Roy N. Alcalay MD, MS, Ziv Gan-Or MD, PhD
{"title":"Plasma Glucosylceramide Levels Are Regulated by ATP10D and Are Not Involved in Parkinson's Disease Pathogenesis","authors":"Emma N. Somerville BSc,&nbsp;Alva James PhD,&nbsp;Christian Beetz PhD,&nbsp;Robert Schwieger PhD,&nbsp;Gal Barrel PhD,&nbsp;Krishna K. Kandaswamy PhD,&nbsp;Marius I. Iurascu PhD,&nbsp;Peter Bauer MD,&nbsp;Michael Ta MS,&nbsp;Hirotaka Iwaki MD, PhD,&nbsp;Konstantin Senkevich MD, PhD,&nbsp;Eric Yu PhD,&nbsp;Roy N. Alcalay MD, MS,&nbsp;Ziv Gan-Or MD, PhD","doi":"10.1002/ana.27219","DOIUrl":"10.1002/ana.27219","url":null,"abstract":"<p><i>GBA1</i> variants and decreased glucocerebrosidase activity are implicated in Parkinson's disease (PD). We investigated the hypothesis that increased levels of glucosylceramide (GlcCer), a main substrate of glucocerebrosidase, are involved in PD pathogenesis. Using multiple genetic methods, we show that ATPase phospholipid transporting 10D (<i>ATP10D</i>), not <i>GBA1</i>, is the main regulator of plasma GlcCer levels, yet it is not involved in PD pathogenesis. Plasma GlcCer levels were associated with PD, but not in a causative manner, and are not predictive of disease status. These results argue against targeting GlcCer in <i>GBA1</i>-PD, and underscore the need to explore alternative mechanisms and biomarkers for PD. ANN NEUROL 2025;97:873–878</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 5","pages":"873-878"},"PeriodicalIF":8.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27219","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Longitudinal Proteomic Profiling of Cognition across an Aerobic Exercise Intervention 有氧运动干预中认知的纵向蛋白质组学分析。
IF 8.1 1区 医学
Annals of Neurology Pub Date : 2025-02-27 DOI: 10.1002/ana.27210
Alison M. H. Donald, Luiz G. N. de Almeida, Mohamed Ziad Dabaja, Isabella Orchard, Kaia Ybema, Veronica Tsegai, Victoria Armstrong, Sophie Smith, Daniel Young, Richard Stewart Longman, Amanda V. Tyndall, Jean M. Rawling, Michael D. Hill, Willis H. Tsai, Ejaife Agbani, Marc J. Poulin, Antoine Dufour
{"title":"Longitudinal Proteomic Profiling of Cognition across an Aerobic Exercise Intervention","authors":"Alison M. H. Donald,&nbsp;Luiz G. N. de Almeida,&nbsp;Mohamed Ziad Dabaja,&nbsp;Isabella Orchard,&nbsp;Kaia Ybema,&nbsp;Veronica Tsegai,&nbsp;Victoria Armstrong,&nbsp;Sophie Smith,&nbsp;Daniel Young,&nbsp;Richard Stewart Longman,&nbsp;Amanda V. Tyndall,&nbsp;Jean M. Rawling,&nbsp;Michael D. Hill,&nbsp;Willis H. Tsai,&nbsp;Ejaife Agbani,&nbsp;Marc J. Poulin,&nbsp;Antoine Dufour","doi":"10.1002/ana.27210","DOIUrl":"10.1002/ana.27210","url":null,"abstract":"<p>The physiological basis of cognitive decline remains largely uncharacterized. We identified a protein panel signature, in living humans, that correlates to improvement in neurocognition over a period of 5 years. Our signature is composed of complement proteins, coagulation cascade, and extracellular matrix regulators. In our cohort, SERPINF1 is associated with greater maximal oxygen uptake after an aerobic exercise intervention. Sleep quality is also a key factor in relation to inter-alpha-trypsin inhibitor heavy chain H2, which was associated with greater sleep efficiency. Additionally, we validate that the coagulation profile of decliners’ plasma contains procoagulant agonists, leading to greater platelet activation. ANN NEUROL 2025;97:1007–1018</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 5","pages":"1007-1018"},"PeriodicalIF":8.1,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27210","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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