Shreeya Kedia, Hao Ji, Ruoqing Feng, Peter Androvic, Lena Spieth, Lu Liu, Jonas Franz, Hanna Zdiarstek, Katrin Perez Anderson, Cem Kaboglu, Qian Liu, Nicola Mattugini, Fatma Cherif, Danilo Prtvar, Ludovico Cantuti-Castelvetri, Arthur Liesz, Martina Schifferer, Christine Stadelmann, Sabina Tahirovic, Ozgun Gokce, Mikael Simons
{"title":"Author Correction: T cell-mediated microglial activation triggers myelin pathology in a mouse model of amyloidosis.","authors":"Shreeya Kedia, Hao Ji, Ruoqing Feng, Peter Androvic, Lena Spieth, Lu Liu, Jonas Franz, Hanna Zdiarstek, Katrin Perez Anderson, Cem Kaboglu, Qian Liu, Nicola Mattugini, Fatma Cherif, Danilo Prtvar, Ludovico Cantuti-Castelvetri, Arthur Liesz, Martina Schifferer, Christine Stadelmann, Sabina Tahirovic, Ozgun Gokce, Mikael Simons","doi":"10.1038/s41593-026-02502-x","DOIUrl":"https://doi.org/10.1038/s41593-026-02502-x","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183445","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":"Alus harbor genetic variants that shape the human cortex.","authors":"Enakshi Sinniah, Alex A Pollen","doi":"10.1038/s41593-026-02492-w","DOIUrl":"https://doi.org/10.1038/s41593-026-02492-w","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166503","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}
Drummond E-Wen McCulloch, Kristian Larsen, Annette Johansen, Kristian H Reveles Jensen, Charlotte Havelund Nykjær, Friederike Holze, Nora Falck, Victor Neufeld, Emilia Steenstrup, Peter Skov-Andersen, Anders Spanggård, Maria Geisler, Paw Patrick Randrup, Peter Steen Jensen, Vladimir Shalgunov, Sys Stybe Johansen, Marie Katrine Klose Nielsen, Thomas Lund Andersen, Dea Siggaard Stenbæk, Claus Svarer, Patrick MacDonald Fisher, Gitte Moos Knudsen
{"title":"Investigating molecular and hemodynamic effects of LSD in the human brain.","authors":"Drummond E-Wen McCulloch, Kristian Larsen, Annette Johansen, Kristian H Reveles Jensen, Charlotte Havelund Nykjær, Friederike Holze, Nora Falck, Victor Neufeld, Emilia Steenstrup, Peter Skov-Andersen, Anders Spanggård, Maria Geisler, Paw Patrick Randrup, Peter Steen Jensen, Vladimir Shalgunov, Sys Stybe Johansen, Marie Katrine Klose Nielsen, Thomas Lund Andersen, Dea Siggaard Stenbæk, Claus Svarer, Patrick MacDonald Fisher, Gitte Moos Knudsen","doi":"10.1038/s41593-026-02462-2","DOIUrl":"https://doi.org/10.1038/s41593-026-02462-2","url":null,"abstract":"<p><p>Lysergic acid diethylamide (LSD) is a potent psychedelic with increasing therapeutic interest, yet qualification of target engagement using in vivo neuroimaging has not yet been performed. Using simultaneous positron emission tomography-magnetic resonance imaging technology, we describe multiple brain actions of LSD in seven healthy volunteers blinded to LSD dose received. Here we show that LSD occupies 5-HT2AR with a high affinity and increases both global cerebral blood flow (CBF) and internal carotid artery flow. LSD also decreases global connectivity, which was negatively associated with changes in CBF. We observe an anticlockwise hysteresis loop between plasma drug levels and subjective effects, suggesting atypical pharmacodynamic mechanisms. We contrast our CBF and global connectivity findings and their relation in a separate cohort of 25 participants administered psilocybin, highlighting key consistencies and differences. By establishing the dose-occupancy relation of LSD in humans, our findings provide insights for the clinical development of psychedelic compounds and demonstrate unique neurophysiological effects that distinguish LSD from psilocybin.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167237","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}
Han Cao, Yifan Fu, Xiaopu Zhou, Yangyang Duan, Fanny C F Ip, Yu Chen, Shenyuan Hu, Si Chai Liu, Timothy C Y Kwok, Kin Y Mok, Tom H Cheung, John Hardy, Amy K Y Fu, Nancy Y Ip
{"title":"Genome-wide analysis of common structural variants in Alzheimer's disease identifies a risk-associated regulatory CCG repeat in FAM193B.","authors":"Han Cao, Yifan Fu, Xiaopu Zhou, Yangyang Duan, Fanny C F Ip, Yu Chen, Shenyuan Hu, Si Chai Liu, Timothy C Y Kwok, Kin Y Mok, Tom H Cheung, John Hardy, Amy K Y Fu, Nancy Y Ip","doi":"10.1038/s41593-026-02481-z","DOIUrl":"https://doi.org/10.1038/s41593-026-02481-z","url":null,"abstract":"<p><p>Although Alzheimer's disease (AD) has a polygenic architecture, with numerous associated single-nucleotide polymorphisms (SNPs) identified, the contribution of structural variants (SVs) is unclear. In this study, using long-read (n = 11) and short-read (n = 3,190) sequencing data from the Chinese population, we show that common SVs contribute to AD heritability beyond common SNPs. We identify an expanded CCG repeat in the FAM193B promoter that shows a genome-wide significant association with increased AD risk (odds ratio = 2.20 per 10-repeat increase, P = 5.5 × 10<sup>-13</sup>). The expanded FAM193B-CCG repeat increases FAM193B expression and mediates the pleiotropic association between brain FAM193B expression and AD risk. Analyses of postmortem human brains and cultured neuronal cells show that elevated neuronal FAM193B expression is associated with DNA damage and cell death-related pathways. These findings establish the common FAM193B-CCG repeat as an AD risk genetic factor and highlight the contribution of common SVs to AD heritability.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166587","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}
Yuan Hou, Yichen Li, Pengyue Zhang, Noah Lorincz-Comi, Dhruv Gohel, Fan Fan, Yunguang Qiu, Jun Yang, Xin Chen, Wenqiang Song, Xiaoyu Yang, Zhibing Tan, Zhigang Liu, Xing Fang, Isabela Rivera Paz, William Martin, Yayan Feng, Yadi Zhou, Jielin Xu, Lijun Dou, Jane Border, Huawei Zhang, Jena' N Mazique, Sung Hee Hwang, Richard J Roman, Tousi Babak, Lynn Bekris, Ehud Karavani, Michael Danziger, Michal Rosen-Zvi, Jonathan L Haines, Haiyuan Yu, Bruce D Hammock, James B Leverenz, Andrew A Pieper, Jeffrey Cummings, Feixiong Cheng
{"title":"Alzheimer's disease target and drug discovery by leveraging multiomics and electronic health data.","authors":"Yuan Hou, Yichen Li, Pengyue Zhang, Noah Lorincz-Comi, Dhruv Gohel, Fan Fan, Yunguang Qiu, Jun Yang, Xin Chen, Wenqiang Song, Xiaoyu Yang, Zhibing Tan, Zhigang Liu, Xing Fang, Isabela Rivera Paz, William Martin, Yayan Feng, Yadi Zhou, Jielin Xu, Lijun Dou, Jane Border, Huawei Zhang, Jena' N Mazique, Sung Hee Hwang, Richard J Roman, Tousi Babak, Lynn Bekris, Ehud Karavani, Michael Danziger, Michal Rosen-Zvi, Jonathan L Haines, Haiyuan Yu, Bruce D Hammock, James B Leverenz, Andrew A Pieper, Jeffrey Cummings, Feixiong Cheng","doi":"10.1038/s41593-026-02472-0","DOIUrl":"10.1038/s41593-026-02472-0","url":null,"abstract":"<p><p>Despite prolific genomic data from individuals with Alzheimer's disease (AD), translation into treatments has lagged. Here we applied Mendelian randomization to multiple AD genome-wide association studies and functional multiomics datasets to nominate druggable targets, identifying 19 targets for individuals of European ancestry and 7 for African ancestry. This included epoxide hydrolase 2 (EPHX2), for which we identified a protective missense variant (p.Arg287Gln). Experiments in induced pluripotent stem cell-derived neurons and cerebral organoids from patients with AD validated the protective role of p.Arg287Gln via reduced levels of EPHX2 and phosphorylated tau (pTau-181). Pharmacological inhibition of EPHX2 improved cognitive performance in the 5xFAD mouse model of AD. Finally, by leveraging electronic health data from 111,680 patients with mild cognitive impairment, we identified 12 drugs associated with reduced AD incidence, including trazodone (targeting ADRA1A) and baclofen (targeting GABBR1). Thus, integrating multiomics data, functional validation and electronic health data identifies new approaches for treating AD.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137844","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}
Danlei Chen,Maya Barton-Zuckerman,Zoe Kross,Philip A. Kragel,Paul W. Savoca,Lawrence L. Wald,Marta Bianciardi,Tor D. Wager,Ji-Kyung Choi,Jiahe Zhang,Karen S. Quigley,Ajay B. Satpute,Lisa Feldman Barrett,Jordan E. Theriault-Brown
{"title":"Modality-specific reactive and predictive responses in the human superior colliculus","authors":"Danlei Chen,Maya Barton-Zuckerman,Zoe Kross,Philip A. Kragel,Paul W. Savoca,Lawrence L. Wald,Marta Bianciardi,Tor D. Wager,Ji-Kyung Choi,Jiahe Zhang,Karen S. Quigley,Ajay B. Satpute,Lisa Feldman Barrett,Jordan E. Theriault-Brown","doi":"10.1038/s41593-026-02480-0","DOIUrl":"https://doi.org/10.1038/s41593-026-02480-0","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"20 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087921","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}
Maria Stavrou,Áine Bríd Heffernan,Roderick N. Carter,Owen Dando,Zoeb Jiwaji,Karen Burr,Jyoti Nanda,David Villarroel-Campos,Alya Masoud Abdelhafid,Justyna Cholewa-Waclaw,Daniel Soong,David Story,Giampietro Schiavo,Giles E. Hardingham,Siddharthan Chandran,Bhuvaneish T. Selvaraj
{"title":"Astrocytes regulate axonal mitochondrial transport deficits in C9ORF72 amyotrophic lateral sclerosis motor neurons","authors":"Maria Stavrou,Áine Bríd Heffernan,Roderick N. Carter,Owen Dando,Zoeb Jiwaji,Karen Burr,Jyoti Nanda,David Villarroel-Campos,Alya Masoud Abdelhafid,Justyna Cholewa-Waclaw,Daniel Soong,David Story,Giampietro Schiavo,Giles E. Hardingham,Siddharthan Chandran,Bhuvaneish T. Selvaraj","doi":"10.1038/s41593-026-02464-0","DOIUrl":"https://doi.org/10.1038/s41593-026-02464-0","url":null,"abstract":"Abstract Disrupted axonal transport and astrocyte dysfunction are implicated in amyotrophic lateral sclerosis (ALS). Here we show these processes are linked—human-induced pluripotent stem-cell-derived astrocytes carrying the C9ORF72 mutation disrupt mitochondrial axonal transport and mitochondrial function in cocultured motor neurons (MNs). Conversely, isogenic gene-corrected astrocytes or boosting astrocytic mitochondrial bioenergetics rescue axonal mitochondrial transport deficits in C9ORF72 MNs. Our results delineate a non-cell-autonomous role for astrocytes in regulating mitochondrial transport along axons in ALS models.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"457 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087922","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}
Melissa Franch,Elizabeth A. Mickiewicz,James L. Belanger,Brad Joiner,Kalman A. Katlowitz,Hanlin Zhu,Ana G. Chavez,Assia Chericoni,Alica M. Goldman,Vaishnav Krishnan,Atul Maheshwari,Danika L. Paulo,Eleonora Bartoli,Suzanne Kemmer,Steven T. Piantadosi,Nicole R. Provenza,Jay A. Hennig,Sameer A. Sheth,Benjamin Y. Hayden
{"title":"Publisher Correction: A population code for semantics in human hippocampus","authors":"Melissa Franch,Elizabeth A. Mickiewicz,James L. Belanger,Brad Joiner,Kalman A. Katlowitz,Hanlin Zhu,Ana G. Chavez,Assia Chericoni,Alica M. Goldman,Vaishnav Krishnan,Atul Maheshwari,Danika L. Paulo,Eleonora Bartoli,Suzanne Kemmer,Steven T. Piantadosi,Nicole R. Provenza,Jay A. Hennig,Sameer A. Sheth,Benjamin Y. Hayden","doi":"10.1038/s41593-026-02501-y","DOIUrl":"https://doi.org/10.1038/s41593-026-02501-y","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"73 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087923","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}
Mingyue Hu, Rodrigo Dalvit, Mauricio Medina-Pizarro, Maximilian Dougherty, Yajun Zhou, Jonathan Barreto-Nieves, Sami Obaid, Arman Afrasiyabi, Smita Krishnaswamy, Alfred P. Kaye, Murat Günel, John H. Krystal, Kevin N. Sheth, Xiaosi Gu, Christopher P. Pittenger, Toby Wise, Eyiyemisi C. Damisah
{"title":"Human claustrum neurons encode uncertainty and prediction errors during aversive learning","authors":"Mingyue Hu, Rodrigo Dalvit, Mauricio Medina-Pizarro, Maximilian Dougherty, Yajun Zhou, Jonathan Barreto-Nieves, Sami Obaid, Arman Afrasiyabi, Smita Krishnaswamy, Alfred P. Kaye, Murat Günel, John H. Krystal, Kevin N. Sheth, Xiaosi Gu, Christopher P. Pittenger, Toby Wise, Eyiyemisi C. Damisah","doi":"10.1038/s41593-026-02475-x","DOIUrl":"https://doi.org/10.1038/s41593-026-02475-x","url":null,"abstract":"Flexible behavior depends on continuous updating of internal models, yet the neural circuits coordinating this process remain poorly understood. The claustrum, which is reciprocally connected to nearly the entire neocortex, is uniquely positioned to influence cortical processing. Here we report single-neuron recordings from the human claustrum during aversive learning, with anterior cingulate cortex and amygdala recordings for comparison. Claustrum and anterior cingulate neurons displayed structured, task-related responses. Distinct subpopulations encoded stimulus onset and action-contingent outcomes, with outcome representations diverging between regions. Critically, both regions encoded model-derived latent variables, including uncertainty and prediction error, but with different temporal profiles; only the anterior cingulate carried uncertainty signals during the intertrial period, whereas both regions encoded uncertainty and prediction error during the active-avoidance period. By contrast, the amygdala showed minimal latent-variable modulation. These findings provide evidence that human claustrum neurons track higher-order cognitive variables not directly observable from sensory input and reveal dissociable roles for the claustrum and anterior cingulate cortex in tracking latent task states.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"45 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087841","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}
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