Pub Date : 2026-03-16DOI: 10.1038/s41582-026-01189-9
Emrah Düzel,Michael R Kreutz
Losing track of personal experiences is a defining feature of Alzheimer disease (AD), arising from the spread of AD pathology through the brain circuits that support episodic memory. In this Review, we explore strategies to improve the function of episodic memory circuits in AD by leveraging the optimized use of neural resources. We introduce the circuit utilization framework, which builds on evidence that synaptic dysfunction, maladaptive responses and deficient adaptive plasticity contribute to episodic memory impairment. The circuit utilization framework posits that by optimizing the utilization of circuit resources, episodic memory function can be partially regained. Our focus includes mitigation of hypoactive and hyperactive synaptic dysfunction, reduction of maladaptive processes and enhancement of brain and cognitive reserve. The circuit utilization framework is grounded in circuit-specific hypotheses that link the component processes of episodic memory to clinical symptoms of memory impairment and AD progression. Its overarching aim is to guide the development of interventions that support episodic memory in people with AD, complementing disease-modifying treatments such as anti-amyloid antibody therapies.
{"title":"Maintaining and regaining episodic memory in Alzheimer disease: a circuit-based perspective.","authors":"Emrah Düzel,Michael R Kreutz","doi":"10.1038/s41582-026-01189-9","DOIUrl":"https://doi.org/10.1038/s41582-026-01189-9","url":null,"abstract":"Losing track of personal experiences is a defining feature of Alzheimer disease (AD), arising from the spread of AD pathology through the brain circuits that support episodic memory. In this Review, we explore strategies to improve the function of episodic memory circuits in AD by leveraging the optimized use of neural resources. We introduce the circuit utilization framework, which builds on evidence that synaptic dysfunction, maladaptive responses and deficient adaptive plasticity contribute to episodic memory impairment. The circuit utilization framework posits that by optimizing the utilization of circuit resources, episodic memory function can be partially regained. Our focus includes mitigation of hypoactive and hyperactive synaptic dysfunction, reduction of maladaptive processes and enhancement of brain and cognitive reserve. The circuit utilization framework is grounded in circuit-specific hypotheses that link the component processes of episodic memory to clinical symptoms of memory impairment and AD progression. Its overarching aim is to guide the development of interventions that support episodic memory in people with AD, complementing disease-modifying treatments such as anti-amyloid antibody therapies.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"59 1","pages":""},"PeriodicalIF":38.1,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147465234","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}
Pub Date : 2026-03-13DOI: 10.1038/s41582-026-01197-9
Heather Wood
{"title":"Uncovering a barrier at the base of the choroid plexus.","authors":"Heather Wood","doi":"10.1038/s41582-026-01197-9","DOIUrl":"https://doi.org/10.1038/s41582-026-01197-9","url":null,"abstract":"","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"127 1","pages":""},"PeriodicalIF":38.1,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446968","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}
Pub Date : 2026-03-11DOI: 10.1038/s41582-026-01191-1
Cenk Ayata,Anders Hougaard,Steven J Schiff,Michel D Ferrari,Jeffrey L Noebels,H Christoph Diener,Martin Lauritzen
Spreading depression is a neurophysiological phenomenon that is observed in the central nervous system of many species, from insects to humans. In essence, spreading depression is a slowly propagating wave of mass depolarization (that is, spreading depolarization), aptly termed a 'brain tsunami', which successively engulfs contiguous brain regions, causing transient neuronal hyperexcitability at its leading edge, followed by complete but reversible neuronal silence lasting minutes. This wave cannot be detected in routine scalp EEG recordings, which contributes to its under-recognized status as a disease biomarker. Here, we present an evidence-based view of spreading depression as a probable cause of characteristic neurological signs and symptoms in numerous neurological conditions. Although migraine aura is a widely recognized manifestation of spreading depression, the clinical signs and symptoms of spreading depressions arising from structural brain pathology have remained an orphan concept with no established name or place in clinical terminology. Therefore, clinicians have long used the term 'migraine aura' to describe the transient neurological manifestations of spreading depression that occur entirely outside of the context of a migraine attack. As migraine is a primary headache disorder not caused by known structural pathology, this terminology is not only erroneous but could also lead to serious misdiagnoses. Consequently, we advocate for the clinical adoption of the more specific mechanistic term spreading depression to describe these clinical episodes. We believe it is imperative to recognize spreading depression as a generic mechanism underlying certain inherited or acquired neurological deficits and to differentiate between structural and non-structural aetiologies, as is done in seizure disorders.
{"title":"Tsunamis hiding in plain sight: spreading depression in clinical neurology.","authors":"Cenk Ayata,Anders Hougaard,Steven J Schiff,Michel D Ferrari,Jeffrey L Noebels,H Christoph Diener,Martin Lauritzen","doi":"10.1038/s41582-026-01191-1","DOIUrl":"https://doi.org/10.1038/s41582-026-01191-1","url":null,"abstract":"Spreading depression is a neurophysiological phenomenon that is observed in the central nervous system of many species, from insects to humans. In essence, spreading depression is a slowly propagating wave of mass depolarization (that is, spreading depolarization), aptly termed a 'brain tsunami', which successively engulfs contiguous brain regions, causing transient neuronal hyperexcitability at its leading edge, followed by complete but reversible neuronal silence lasting minutes. This wave cannot be detected in routine scalp EEG recordings, which contributes to its under-recognized status as a disease biomarker. Here, we present an evidence-based view of spreading depression as a probable cause of characteristic neurological signs and symptoms in numerous neurological conditions. Although migraine aura is a widely recognized manifestation of spreading depression, the clinical signs and symptoms of spreading depressions arising from structural brain pathology have remained an orphan concept with no established name or place in clinical terminology. Therefore, clinicians have long used the term 'migraine aura' to describe the transient neurological manifestations of spreading depression that occur entirely outside of the context of a migraine attack. As migraine is a primary headache disorder not caused by known structural pathology, this terminology is not only erroneous but could also lead to serious misdiagnoses. Consequently, we advocate for the clinical adoption of the more specific mechanistic term spreading depression to describe these clinical episodes. We believe it is imperative to recognize spreading depression as a generic mechanism underlying certain inherited or acquired neurological deficits and to differentiate between structural and non-structural aetiologies, as is done in seizure disorders.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"19 1","pages":""},"PeriodicalIF":38.1,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147393832","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}
Pub Date : 2026-03-10DOI: 10.1038/s41582-026-01190-2
Marta de Lucas Sanz,Simone P Niclou,Anna Golebiewska
Precision medicine in neuro-oncology hinges on our ability to decode the molecular and functional complexity of brain tumours. These tumours are highly heterogeneous and dynamic ecosystems that remain challenging to replicate with traditional experimental models. Organoids have emerged as next-generation tools for capturing the diversity of brain tumours in a clinically relevant context. Here, we review advances in applying organoids as tumour avatars to foster precision medicine. We assess current methodologies for generating organoids from various brain tumour types and illustrate how these models have enhanced mechanistic insight into tumour initiation, progression and resistance to treatment. Furthermore, we explore their translational potential in functional drug screening and treatment stratification, offering a powerful preclinical and co-clinical platform with which to personalize neuro-oncology.
{"title":"Modelling brain tumours with organoids: towards precision medicine in neuro-oncology.","authors":"Marta de Lucas Sanz,Simone P Niclou,Anna Golebiewska","doi":"10.1038/s41582-026-01190-2","DOIUrl":"https://doi.org/10.1038/s41582-026-01190-2","url":null,"abstract":"Precision medicine in neuro-oncology hinges on our ability to decode the molecular and functional complexity of brain tumours. These tumours are highly heterogeneous and dynamic ecosystems that remain challenging to replicate with traditional experimental models. Organoids have emerged as next-generation tools for capturing the diversity of brain tumours in a clinically relevant context. Here, we review advances in applying organoids as tumour avatars to foster precision medicine. We assess current methodologies for generating organoids from various brain tumour types and illustrate how these models have enhanced mechanistic insight into tumour initiation, progression and resistance to treatment. Furthermore, we explore their translational potential in functional drug screening and treatment stratification, offering a powerful preclinical and co-clinical platform with which to personalize neuro-oncology.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"52 1","pages":""},"PeriodicalIF":38.1,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147383291","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}
Pub Date : 2026-03-05DOI: 10.1038/s41582-026-01182-2
Beth Grimsey
Beth Grimsey lives with relapsing–remitting multiple sclerosis (MS) and is the Research Programme Manager at the MS Society in the UK. In this World View, she reflects on the uncertainty of MS, the ripple effects in families and the need for healthcare providers to communicate the knowns and unknowns.
{"title":"We need to talk about risk in multiple sclerosis","authors":"Beth Grimsey","doi":"10.1038/s41582-026-01182-2","DOIUrl":"10.1038/s41582-026-01182-2","url":null,"abstract":"Beth Grimsey lives with relapsing–remitting multiple sclerosis (MS) and is the Research Programme Manager at the MS Society in the UK. In this World View, she reflects on the uncertainty of MS, the ripple effects in families and the need for healthcare providers to communicate the knowns and unknowns.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"22 3","pages":"137-137"},"PeriodicalIF":33.1,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147352899","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}
Pub Date : 2026-03-04DOI: 10.1038/s41582-026-01193-z
Lisanne J Dommershuijsen,Sirwan K L Darweesh,Bastiaan R Bloem
{"title":"Epidemiological principles behind worldwide growth of Parkinson disease - a bathtub analogy.","authors":"Lisanne J Dommershuijsen,Sirwan K L Darweesh,Bastiaan R Bloem","doi":"10.1038/s41582-026-01193-z","DOIUrl":"https://doi.org/10.1038/s41582-026-01193-z","url":null,"abstract":"","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"1 1","pages":""},"PeriodicalIF":38.1,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350293","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}
Pub Date : 2026-02-13DOI: 10.1038/s41582-026-01185-z
Eduardo Tolosa, Werner Poewe, Alastair J. Noyce, Per Svenningsson, Philipp Mahlknecht, Maria Jose Marti
The current clinical diagnostic criteria for Parkinson disease (PD) have limitations and are inherently insensitive to the earliest stages of disease, when classical motor signs can be absent. Imaging and genetic tests are currently used to support or establish a diagnosis of PD, but no validated biomarker-based diagnostic framework currently exists. Substantial progress has been made in the field of molecular disease markers, most notably with the development and validation of seed amplification assays (SAAs), which enable detection of very low levels of pathological α-synuclein in the cerebrospinal fluid and other biofluids and tissue. In this Review, we discuss the potential of α-synuclein SAAs and other biomarkers to improve diagnostic accuracy and enable earlier diagnosis of PD. We consider biological disease definitions that have been proposed on the basis of these biomarkers, highlighting their merits, limitations and implications for PD research and clinical management. Research is ongoing to determine the predictive value of PD biomarkers in healthy people and people with prodromal PD and to develop markers that are sensitive to disease progression, both of which are key for implementation of trials involving drugs designed to modify or prevent disease. Integrating clinical, genetic, molecular and imaging biomarkers should enable earlier, more accurate diagnosis of PD and characterization of PD subtypes, thereby enabling personalized treatment to slow or even prevent PD. Clinical diagnostic criteria for Parkinson disease (PD) have limitations, but no validated biomarker-based diagnostic framework currently exists. In this Review, Tolosa et al. examine progress towards biomarker-based diagnosis of PD, focusing on α-synuclein seed amplification assays alongside molecular, imaging and genetic markers.
{"title":"Towards biomarker-based diagnosis of Parkinson disease","authors":"Eduardo Tolosa, Werner Poewe, Alastair J. Noyce, Per Svenningsson, Philipp Mahlknecht, Maria Jose Marti","doi":"10.1038/s41582-026-01185-z","DOIUrl":"10.1038/s41582-026-01185-z","url":null,"abstract":"The current clinical diagnostic criteria for Parkinson disease (PD) have limitations and are inherently insensitive to the earliest stages of disease, when classical motor signs can be absent. Imaging and genetic tests are currently used to support or establish a diagnosis of PD, but no validated biomarker-based diagnostic framework currently exists. Substantial progress has been made in the field of molecular disease markers, most notably with the development and validation of seed amplification assays (SAAs), which enable detection of very low levels of pathological α-synuclein in the cerebrospinal fluid and other biofluids and tissue. In this Review, we discuss the potential of α-synuclein SAAs and other biomarkers to improve diagnostic accuracy and enable earlier diagnosis of PD. We consider biological disease definitions that have been proposed on the basis of these biomarkers, highlighting their merits, limitations and implications for PD research and clinical management. Research is ongoing to determine the predictive value of PD biomarkers in healthy people and people with prodromal PD and to develop markers that are sensitive to disease progression, both of which are key for implementation of trials involving drugs designed to modify or prevent disease. Integrating clinical, genetic, molecular and imaging biomarkers should enable earlier, more accurate diagnosis of PD and characterization of PD subtypes, thereby enabling personalized treatment to slow or even prevent PD. Clinical diagnostic criteria for Parkinson disease (PD) have limitations, but no validated biomarker-based diagnostic framework currently exists. In this Review, Tolosa et al. examine progress towards biomarker-based diagnosis of PD, focusing on α-synuclein seed amplification assays alongside molecular, imaging and genetic markers.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"22 3","pages":"139-151"},"PeriodicalIF":33.1,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195234","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}
Pub Date : 2026-02-11DOI: 10.1038/s41582-026-01186-y
Sam Parnia, Jignesh Patel, Erik Kulstad, Rebecca Spiegel, Stephen G. Post, Sanam Alilou, Benjamin M. Bloom, Natalia Leontovich, Anelly M. Gonzales, Tara Keshavarz, Charles D. Deakin
{"title":"Recalled experiences of death: need for empirical research without prejudice","authors":"Sam Parnia, Jignesh Patel, Erik Kulstad, Rebecca Spiegel, Stephen G. Post, Sanam Alilou, Benjamin M. Bloom, Natalia Leontovich, Anelly M. Gonzales, Tara Keshavarz, Charles D. Deakin","doi":"10.1038/s41582-026-01186-y","DOIUrl":"10.1038/s41582-026-01186-y","url":null,"abstract":"","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"22 3","pages":"196-197"},"PeriodicalIF":33.1,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146166003","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}
Pub Date : 2026-02-11DOI: 10.1038/s41582-026-01188-w
Lisa Kiani
The natural migration pathway of CNS immune cells can be harnessed to deliver therapy to brain lesions in acute stroke, bypassing the blood–brain barrier (BBB), according to a new study published in Cell.
{"title":"Immune gateways bypass blood–brain barrier for drug delivery in stroke","authors":"Lisa Kiani","doi":"10.1038/s41582-026-01188-w","DOIUrl":"10.1038/s41582-026-01188-w","url":null,"abstract":"The natural migration pathway of CNS immune cells can be harnessed to deliver therapy to brain lesions in acute stroke, bypassing the blood–brain barrier (BBB), according to a new study published in Cell.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"22 3","pages":"138-138"},"PeriodicalIF":33.1,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146166060","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：