Brain最新文献

{"title":"Plasma periaxin is a biomarker of peripheral nerve demyelination","authors":"Roberto Bellanti, Ryan Y S Keh, Stephen Keddie, Michael K L Chou, Mariya Misheva, Duncan Smyth, Georgios Baskozos, Kaminie Moodley, Melanie S Hart, Alexander Davies, Mary M Reilly, Simon Rinaldi, Michael P Lunn","doi":"10.1093/brain/awaf234","DOIUrl":"https://doi.org/10.1093/brain/awaf234","url":null,"abstract":"Assessing disease progression and informing clinical trials in peripheral neuropathy would benefit from objective and responsive fluid biomarkers closely linked to disease biology. This is particularly important in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain-Barré syndrome (GBS), the most common inflammatory neuropathies, where reliable biomarkers of peripheral demyelination would help identify, and potentially measure, active disease and responses to treatment. We postulated that periaxin, a protein exclusively expressed by myelinating Schwann cells, could serve as a fluid biomarker of demyelinating peripheral neuropathy. We developed a Simoa-based immunoassay to measure plasma periaxin in patients with CIDP (n = 45, including longitudinal samples across a discovery cohort and a validation cohort, for a total of 77 time points), GBS (n = 30, 66 time points), Charcot-Marie-Tooth disease (CMT, n = 20), central nervous system (CNS) disease controls with multiple sclerosis (MS, n = 30), and healthy controls (HC, n = 30). We also evaluated whether periaxin is released in myelinating cocultures following immune-mediated demyelination and axonal damage, comparing results with uninjured cultures. Plasma periaxin effectively distinguishes peripheral from central nervous system diseases, with significantly elevated levels in CIDP, GBS, and CMT, but not in CNS disease or healthy controls (all P < 0.01). In CIDP, periaxin discriminates patients with active disease from those with inactive disease (P < 0.0001), and plasma levels decrease following treatment with intravenous immunoglobulin (IVIg). Elevated periaxin strongly predicts clinical worsening at 1 year [sensitivity 99%, specificity 72%, area under the curve (AUC) 0.86 (95% C.I. 0.67–1)]. In GBS, peak levels of plasma periaxin and the ratio of periaxin to axonal biomarkers [neurofilament light chain (NfL) and peripherin] discriminate most cases of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) from acute motor axonal neuropathy (AMAN), as classified by electrophysiology (sensitivity 100%, specificity 86%, AUC = 0.94, 95% CI 0.81-1). Serial measurements showed that plasma periaxin levels peak 2 to 3 weeks after GBS symptom onset, followed by a gradual decline in the weeks thereafter. In vitro, periaxin is higher following immune-mediated demyelination compared to axonal damage and control conditions. Plasma periaxin is a biomarker of peripheral nerve demyelination. Combined with axonal fluid biomarkers and existing clinical scales, periaxin has the potential to improve the clinical management of peripheral neuropathies, accelerating advances in care and experimental research.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"23 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513184","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}

{"title":"The aphantasia paradox: a Sartrean update","authors":"Margherita Arcangeli, Paolo Bartolomeo","doi":"10.1093/brain/awaf233","DOIUrl":"https://doi.org/10.1093/brain/awaf233","url":null,"abstract":"Neuroscientific research into mental imagery often relies on David Hume’s view of visual imagination as weak perception. Arcangeli & Bartolomeo argue that Jean-Paul Sartre’s alternative framework—supported by recent findings on aphantasia—offers a more conceptually and empirically robust approach.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"70 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503735","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}

{"title":"The duality of disease: the Alzheimer’s disease dilemma through the lens of nosos and asthenia","authors":"Nikolaos Scarmeas, Adrián Noriega De La Colina","doi":"10.1093/brain/awaf239","DOIUrl":"https://doi.org/10.1093/brain/awaf239","url":null,"abstract":"Scarmeas & Noriega De La Colina use the ancient Greek concepts of nosos (biological disease) and asthenia (functional decline) to frame the shift in Alzheimer’s disease diagnosis from clinical symptoms to biomarkers, calling for better public understanding of both biological presence and lived experience.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"10 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500549","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}

{"title":"Expanding the clinical spectrum of RAB3A: from cerebellar ataxia to spastic paraplegia.","authors":"Charlotte Mouraux, Jean-Loup Méreaux, Claire-Sophie Davoine, Léna Guillot Noel, Alexis Brice, Alexandra Durr, Giulia Coarelli","doi":"10.1093/brain/awaf236","DOIUrl":"https://doi.org/10.1093/brain/awaf236","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504775","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}

{"title":"Expanding the clinical spectrum of RAB3A: from cerebellar ataxia to spastic paraplegia.","authors":"Charlotte Mouraux,Jean-Loup Méreaux,Claire-Sophie Davoine,Léna Guillot Noel,Alexis Brice,Alexandra Durr,Giulia Coarelli","doi":"10.1093/brain/awaf236","DOIUrl":"https://doi.org/10.1093/brain/awaf236","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":"13 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504621","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}

{"title":"Correction to: Accumulation of oligomer-prone α-synuclein exacerbates synaptic and neuronal degeneration in vivo.","authors":"","doi":"10.1093/brain/awaf232","DOIUrl":"https://doi.org/10.1093/brain/awaf232","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":"639 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478762","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}

{"title":"MED27 function is essential for cerebellar development and motor behaviour.","authors":"Sabrina Maher, Eloise Langlois Bernard, Charlotte Zaouter, Shunmoogum A Patten","doi":"10.1093/brain/awaf237","DOIUrl":"https://doi.org/10.1093/brain/awaf237","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511518","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}

{"title":"Twins with temporal lobe epilepsy: genetic contributions to hippocampal sclerosis and other subtypes.","authors":"Yew Li Dang, Kate Esnault, Gregory Fitt, Terence J O'Brien, Graeme D Jackson, Piero Perucca, Samuel F Berkovic","doi":"10.1093/brain/awaf209","DOIUrl":"https://doi.org/10.1093/brain/awaf209","url":null,"abstract":"<p><p>Temporal lobe epilepsy is the most common focal epilepsy in adults. While temporal lobe epilepsy was historically perceived to have a largely acquired aetiology, growing evidence points to important genetic contributions. There are several temporal lobe epilepsy subtypes, including mesial temporal lobe epilepsy with or without hippocampal sclerosis, but the relative genetic contributions to each of these subtypes have not been directly studied. In this study, we use the classical twin model in 80 twin pairs where at least one twin had temporal lobe epilepsy. We assessed the genetic contribution to various subtypes [lesional temporal lobe epilepsy, non-lesional temporal lobe epilepsy, mesial temporal lobe epilepsy (with or without hippocampal sclerosis), lateral temporal lobe epilepsy, and non-localized temporal lobe epilepsy], by analysing the concordance for temporal lobe epilepsy in monozygotic twins compared to dizygotic twins. In the 10 monozygotic pairs where at least one twin had hippocampal sclerosis, we searched for within-pair acquired differences between affected and unaffected individuals. There was an excess of monozygotic pairs concordant for temporal lobe epilepsy compared to dizygotic pairs (17/47 concordant monozygotic vs 0/33 concordant dizygotic, p<0.05). This supports a genetic contribution to temporal lobe epilepsy, but notably this concordance was driven by non-lesional temporal lobe epilepsy cases, particularly mesial temporal lobe epilepsy without hippocampal sclerosis (14/22 concordant monozygotic vs 0/11 concordant dizygotic, p<0.05). No concordant monozygotic or dizygotic pairs were observed in the lesional temporal lobe epilepsy (n=8) and non-localized temporal lobe epilepsy (n=15) groups. The concordance for temporal lobe epilepsy in monozygotic twins with mesial temporal lobe epilepsy with hippocampal sclerosis was much lower (2/10 concordant monozygotic vs 0/9 concordant dizygotic, p=1), suggesting a lesser contribution from germline genetic causes to mesial temporal lobe epilepsy with hippocampal sclerosis. Eight monozygotic twin pairs were discordant for hippocampal sclerosis. In four of these pairs, both twins had febrile seizures, but hippocampal sclerosis was only present in the twin who had prolonged seizures. The two monozygotic twin pairs concordant for hippocampal sclerosis had clinical neurofibromatosis type 1 with pathogenic germline NF1 variants. Our findings confirm a germline genetic component in temporal lobe epilepsy, strongest in mesial temporal lobe epilepsy without hippocampal sclerosis and present in lateral temporal lobe epilepsy but absent in lesional and non-localized temporal lobe epilepsy. In our mesial temporal lobe epilepsy with hippocampal sclerosis twins, we found both genetic factors (NF1) and prolonged febrile seizures contributed to the aetiology of hippocampal sclerosis.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511519","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}

{"title":"The aphantasia paradox: a Sartrean update.","authors":"Margherita Arcangeli, Paolo Bartolomeo","doi":"10.1093/brain/awaf233","DOIUrl":"https://doi.org/10.1093/brain/awaf233","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504777","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}

{"title":"Extreme exercise in males is linked to mTOR signalling and onset of amyotrophic lateral sclerosis.","authors":"David O'Brien, Elham Alhathli, Ceryl Harwood, Debarati Bhattacharya, Kriti Gupta, Thomas Julian, Marcel Weinreich, Ryan J H West, Dennis Wang, Ross P Byrne, Russell L McLaughlin, Joanne Wuu, Michael Benatar, Johnathan Cooper-Knock, Pamela J Shaw","doi":"10.1093/brain/awaf235","DOIUrl":"https://doi.org/10.1093/brain/awaf235","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is thought to be caused by interaction between genetic and environmental factors leading to motor neuron (MN) degeneration. Physical exercise has been linked to ALS but controversy remains. A key question is to determine which individuals might be at risk of exercise-associated ALS, because unnecessary avoidance of exercise could be harmful. We implemented complementary strategies including Mendelian randomization and multiple questionnaire-based measures of physical exercise in different cohorts. We include a prospective study in UK Biobank participants where we could test for a relationship between exercise and the timing of future ALS symptom onset. To interrogate the molecular basis of our observations we performed a genetic association study of 'extreme' exercise, equivalent to >6 hours of strenuous exercise or >12 hours of any leisure-time exercise per week. Our data suggest that the link between increased physical exercise and ALS is particularly important for males who perform the most activity; with no evidence of a link in females. We determined that extreme exercise in males is associated with loss-of-function genetic variants within a number of mammalian target of rapamycin (mTOR) signalling genes that are also differentially expressed in ALS spinal cord. Activity-induced mTOR signalling has been shown to selectively benefit MN. Therefore, our findings could imply that moderate exercise is neuroprotective via enhanced mTOR signalling, but extreme exercise in men is associated with neurotoxicity and ALS via a failure of this mechanism. There was no significant overlap between genes associated with extreme exercise and those associated with ALS risk, consistent with a true gene-environment interaction rather than a shared genetic basis. We are not yet able to make individual-level recommendations regarding exercise and risk of ALS, but our conclusions should focus future investigation.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511517","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}