Pub Date : 2024-07-09DOI: 10.1038/s41582-024-00994-4
Heather Wood
{"title":"Diabetes could hasten MCI-to-AD conversion","authors":"Heather Wood","doi":"10.1038/s41582-024-00994-4","DOIUrl":"10.1038/s41582-024-00994-4","url":null,"abstract":"","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":null,"pages":null},"PeriodicalIF":28.2,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559323","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 : 2024-07-04DOI: 10.1038/s41582-024-00991-7
Sarah M. Jacob, Sukyoung Lee, Seung Hyun Kim, Keith A. Sharkey, Gerald Pfeffer, Minh Dang Nguyen
Amyotrophic lateral sclerosis (ALS) is the most common form of human motor neuron disease. It is characterized by the progressive degeneration of upper and lower motor neurons, leading to generalized motor weakness and, ultimately, respiratory paralysis and death within 3–5 years. The disease is shaped by genetics, age, sex and environmental stressors, but no cure or routine biomarkers exist for the disease. Male individuals have a higher propensity to develop ALS, and a different manifestation of the disease phenotype, than female individuals. However, the mechanisms underlying these sex differences remain a mystery. In this Review, we summarize the epidemiology of ALS, examine the sexually dimorphic presentation of the disease and highlight the genetic variants and molecular pathways that might contribute to sex differences in humans and animal models of ALS. We advance the idea that sexual dimorphism in ALS arises from the interactions between the CNS and peripheral organs, involving vascular, metabolic, endocrine, musculoskeletal and immune systems, which are strikingly different between male and female individuals. Finally, we review the response to treatments in ALS and discuss the potential to implement future personalized therapeutic strategies for the disease. Amyotrophic lateral sclerosis (ALS) differs considerably in prevalence and manifestation between sexes. This Review summarizes sexual dimorphism in the epidemiology, clinical presentation and disease mechanisms of ALS and explores the role of brain–body interactions in driving sex-dependent pathogenesis.
肌萎缩侧索硬化症（ALS）是人类运动神经元疾病中最常见的一种。其特征是上下运动神经元逐渐退化，导致全身运动无力，最终导致呼吸麻痹，并在 3-5 年内死亡。这种疾病受遗传、年龄、性别和环境压力等因素的影响，但目前还没有治愈这种疾病的方法或常规生物标志物。与女性相比，男性更容易患上渐冻人症，其疾病表型的表现也与女性不同。然而，这些性别差异的内在机制仍是一个谜。在这篇综述中，我们总结了 ALS 的流行病学，研究了该疾病的性别二形表现，并强调了可能导致人类和 ALS 动物模型性别差异的基因变异和分子途径。我们提出的观点是，肌萎缩性脊髓侧索硬化症的性别双态性源于中枢神经系统和外周器官之间的相互作用，涉及血管、代谢、内分泌、肌肉骨骼和免疫系统，这些系统在男性和女性个体之间存在显著差异。最后，我们回顾了 ALS 的治疗反应，并讨论了未来对该疾病实施个性化治疗策略的可能性。
{"title":"Brain–body mechanisms contribute to sexual dimorphism in amyotrophic lateral sclerosis","authors":"Sarah M. Jacob, Sukyoung Lee, Seung Hyun Kim, Keith A. Sharkey, Gerald Pfeffer, Minh Dang Nguyen","doi":"10.1038/s41582-024-00991-7","DOIUrl":"10.1038/s41582-024-00991-7","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is the most common form of human motor neuron disease. It is characterized by the progressive degeneration of upper and lower motor neurons, leading to generalized motor weakness and, ultimately, respiratory paralysis and death within 3–5 years. The disease is shaped by genetics, age, sex and environmental stressors, but no cure or routine biomarkers exist for the disease. Male individuals have a higher propensity to develop ALS, and a different manifestation of the disease phenotype, than female individuals. However, the mechanisms underlying these sex differences remain a mystery. In this Review, we summarize the epidemiology of ALS, examine the sexually dimorphic presentation of the disease and highlight the genetic variants and molecular pathways that might contribute to sex differences in humans and animal models of ALS. We advance the idea that sexual dimorphism in ALS arises from the interactions between the CNS and peripheral organs, involving vascular, metabolic, endocrine, musculoskeletal and immune systems, which are strikingly different between male and female individuals. Finally, we review the response to treatments in ALS and discuss the potential to implement future personalized therapeutic strategies for the disease. Amyotrophic lateral sclerosis (ALS) differs considerably in prevalence and manifestation between sexes. This Review summarizes sexual dimorphism in the epidemiology, clinical presentation and disease mechanisms of ALS and explores the role of brain–body interactions in driving sex-dependent pathogenesis.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":null,"pages":null},"PeriodicalIF":28.2,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141521513","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 : 2024-07-04DOI: 10.1038/s41582-024-00992-6
Jiwon Oh, Amit Bar-Or
Immunological profiling has revealed biological signatures of multiple sclerosis (MS) that could help with early, accurate diagnosis of the disease and with identifying disease subtypes that could inform treatment decisions. The findings are important steps along the path towards precision medicine for people with MS.
{"title":"Precision neuroimmunology in multiple sclerosis — the horizon is near","authors":"Jiwon Oh, Amit Bar-Or","doi":"10.1038/s41582-024-00992-6","DOIUrl":"10.1038/s41582-024-00992-6","url":null,"abstract":"Immunological profiling has revealed biological signatures of multiple sclerosis (MS) that could help with early, accurate diagnosis of the disease and with identifying disease subtypes that could inform treatment decisions. The findings are important steps along the path towards precision medicine for people with MS.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":null,"pages":null},"PeriodicalIF":28.2,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141521512","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 : 2024-07-01DOI: 10.1038/s41582-024-00981-9
Cecile C. de Vos, Kaare Meier
Spinal cord stimulation is an invasive therapy for chronic neuropathic pain, usually used as a last-resort treatment when all other treatments have been tried and failed. The clinical value of the therapy has been much debated in recent years; here, we summarize the therapy and discuss the core controversies. Spinal cord stimulation is seen as a last-resort therapy for the treatment of chronic pain. Controversies surrounding the treatment might be addressed through collaborative efforts to conduct innovative clinical trials and reach consensus on treatment guidelines.
{"title":"Spinal cord stimulation for the treatment of chronic pain","authors":"Cecile C. de Vos, Kaare Meier","doi":"10.1038/s41582-024-00981-9","DOIUrl":"10.1038/s41582-024-00981-9","url":null,"abstract":"Spinal cord stimulation is an invasive therapy for chronic neuropathic pain, usually used as a last-resort treatment when all other treatments have been tried and failed. The clinical value of the therapy has been much debated in recent years; here, we summarize the therapy and discuss the core controversies. Spinal cord stimulation is seen as a last-resort therapy for the treatment of chronic pain. Controversies surrounding the treatment might be addressed through collaborative efforts to conduct innovative clinical trials and reach consensus on treatment guidelines.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":null,"pages":null},"PeriodicalIF":28.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475336","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 : 2024-07-01DOI: 10.1038/s41582-024-00975-7
Raúl Martínez-Fernández
Similar to any innovation that disrupts the status quo, the advent of magnetic resonance-guided focused ultrasound in neurology was accompanied by controversy and debate. However, evidence suggests that this therapeutic tool, which is already widely used to treat tremor and Parkinson disease, is gaining acceptance and will become a viable therapeutic option for various other neurological conditions in the near future.
{"title":"Focused ultrasound brain therapy is a new tool in the box","authors":"Raúl Martínez-Fernández","doi":"10.1038/s41582-024-00975-7","DOIUrl":"10.1038/s41582-024-00975-7","url":null,"abstract":"Similar to any innovation that disrupts the status quo, the advent of magnetic resonance-guided focused ultrasound in neurology was accompanied by controversy and debate. However, evidence suggests that this therapeutic tool, which is already widely used to treat tremor and Parkinson disease, is gaining acceptance and will become a viable therapeutic option for various other neurological conditions in the near future.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":null,"pages":null},"PeriodicalIF":28.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475156","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 : 2024-06-30DOI: 10.1038/s41582-024-00987-3
Nebojša Malešević, Christian Antfolk
Advanced sensory feedback from upper limb prostheses would provide multiple benefits to people with upper limb amputations, but achieving functional and natural-feeling sensation is technologically challenging. Advances are being made with invasive and non-invasive stimulation approaches, but considerable challenges need to be addressed with technological innovation.
{"title":"Sensory feedback in upper limb prosthetics: advances and challenges","authors":"Nebojša Malešević, Christian Antfolk","doi":"10.1038/s41582-024-00987-3","DOIUrl":"10.1038/s41582-024-00987-3","url":null,"abstract":"Advanced sensory feedback from upper limb prostheses would provide multiple benefits to people with upper limb amputations, but achieving functional and natural-feeling sensation is technologically challenging. Advances are being made with invasive and non-invasive stimulation approaches, but considerable challenges need to be addressed with technological innovation.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":null,"pages":null},"PeriodicalIF":28.2,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141463915","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 : 2024-06-30DOI: 10.1038/s41582-024-00980-w
Aurore Thibaut, Géraldine Martens
Neuromodulation represents a promising approach for promoting neural plasticity following a brain injury, especially for non-communicative patients with prolonged disorders of consciousness. However, so far, the outcomes have been limited and inconsistent, driving researchers to explore alternative strategies to improve the efficacy of brain stimulation techniques.
{"title":"Neuromodulation for severe brain injury: time for a paradigm shift?","authors":"Aurore Thibaut, Géraldine Martens","doi":"10.1038/s41582-024-00980-w","DOIUrl":"10.1038/s41582-024-00980-w","url":null,"abstract":"Neuromodulation represents a promising approach for promoting neural plasticity following a brain injury, especially for non-communicative patients with prolonged disorders of consciousness. However, so far, the outcomes have been limited and inconsistent, driving researchers to explore alternative strategies to improve the efficacy of brain stimulation techniques.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":null,"pages":null},"PeriodicalIF":28.2,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141463931","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 : 2024-06-29DOI: 10.1038/s41582-024-00990-8
Friedhelm C. Hummel, Maximilian J. Wessel
Recently developed non-invasive deep brain stimulation methods have sufficient focal specificity to target deep brain structures. These techniques show particular promise as treatment strategies for neuropsychiatric disorders in which deep brain structures have critical roles in pathophysiology or in mediating recovery. A non-invasive technique using transcranial electrical stimulation offers an improvement in focality over other non-invasive techniques, presenting an opportunity to target deep brain structures for the treatment of neurological disorders.
{"title":"Non-invasive deep brain stimulation: interventional targeting of deep brain areas in neurological disorders","authors":"Friedhelm C. Hummel, Maximilian J. Wessel","doi":"10.1038/s41582-024-00990-8","DOIUrl":"10.1038/s41582-024-00990-8","url":null,"abstract":"Recently developed non-invasive deep brain stimulation methods have sufficient focal specificity to target deep brain structures. These techniques show particular promise as treatment strategies for neuropsychiatric disorders in which deep brain structures have critical roles in pathophysiology or in mediating recovery. A non-invasive technique using transcranial electrical stimulation offers an improvement in focality over other non-invasive techniques, presenting an opportunity to target deep brain structures for the treatment of neurological disorders.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":null,"pages":null},"PeriodicalIF":28.2,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141462687","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 : 2024-06-29DOI: 10.1038/s41582-024-00976-6
Irena Rektorová
Some device-based non-invasive brain stimulation methods have been recommended as probably effective for cognitive treatment in Alzheimer disease. New targets and novel transcranial electrical stimulation techniques enable physiology-inspired modulation of oscillatory activity and precise targeting of deep brain structures. The use of non-invasive brain stimulation techniques to treat mild cognitive impairment and dementia in Alzheimer disease is expanding. Trials have produced varying results depending on the differing stimulation techniques, targeted brain regions and degrees of cognitive impairment among the treated cohorts.
{"title":"Non-invasive stimulation for treating cognitive impairment in Alzheimer disease","authors":"Irena Rektorová","doi":"10.1038/s41582-024-00976-6","DOIUrl":"10.1038/s41582-024-00976-6","url":null,"abstract":"Some device-based non-invasive brain stimulation methods have been recommended as probably effective for cognitive treatment in Alzheimer disease. New targets and novel transcranial electrical stimulation techniques enable physiology-inspired modulation of oscillatory activity and precise targeting of deep brain structures. The use of non-invasive brain stimulation techniques to treat mild cognitive impairment and dementia in Alzheimer disease is expanding. Trials have produced varying results depending on the differing stimulation techniques, targeted brain regions and degrees of cognitive impairment among the treated cohorts.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":null,"pages":null},"PeriodicalIF":28.2,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141462718","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 : 2024-06-21DOI: 10.1038/s41582-024-00988-2
Rosemary J. Jackson, Bradley T. Hyman, Alberto Serrano-Pozo
For the past three decades, apolipoprotein E (APOE) has been known as the single greatest genetic modulator of sporadic Alzheimer disease (AD) risk, influencing both the average age of onset and the lifetime risk of developing AD. The APOEε4 allele significantly increases AD risk, whereas the ε2 allele is protective relative to the most common ε3 allele. However, large differences in effect size exist across ethnoracial groups that are likely to depend on both global genetic ancestry and local genetic ancestry, as well as gene–environment interactions. Although early studies linked APOE to amyloid-β — one of the two culprit aggregation-prone proteins that define AD — in the past decade, mounting work has associated APOE with other neurodegenerative proteinopathies and broader ageing-related brain changes, such as neuroinflammation, energy metabolism failure, loss of myelin integrity and increased blood–brain barrier permeability, with potential implications for longevity and resilience to pathological protein aggregates. Novel mouse models and other technological advances have also enabled a number of therapeutic approaches aimed at either attenuating the APOEε4-linked increased AD risk or enhancing the APOEε2-linked AD protection. This Review summarizes this progress and highlights areas for future research towards the development of APOE-directed therapeutics. Apolipoprotein E (APOE) is the greatest genetic modulator of sporadic Alzheimer disease risk. This Review provides a comprehensive update on our current knowledge of the genetics of APOE and its role in Alzheimer and other neurodegenerative diseases, and summarizes emerging APOE-targeted therapies designed to prevent or slow down Alzheimer disease.
{"title":"Multifaceted roles of APOE in Alzheimer disease","authors":"Rosemary J. Jackson, Bradley T. Hyman, Alberto Serrano-Pozo","doi":"10.1038/s41582-024-00988-2","DOIUrl":"10.1038/s41582-024-00988-2","url":null,"abstract":"For the past three decades, apolipoprotein E (APOE) has been known as the single greatest genetic modulator of sporadic Alzheimer disease (AD) risk, influencing both the average age of onset and the lifetime risk of developing AD. The APOEε4 allele significantly increases AD risk, whereas the ε2 allele is protective relative to the most common ε3 allele. However, large differences in effect size exist across ethnoracial groups that are likely to depend on both global genetic ancestry and local genetic ancestry, as well as gene–environment interactions. Although early studies linked APOE to amyloid-β — one of the two culprit aggregation-prone proteins that define AD — in the past decade, mounting work has associated APOE with other neurodegenerative proteinopathies and broader ageing-related brain changes, such as neuroinflammation, energy metabolism failure, loss of myelin integrity and increased blood–brain barrier permeability, with potential implications for longevity and resilience to pathological protein aggregates. Novel mouse models and other technological advances have also enabled a number of therapeutic approaches aimed at either attenuating the APOEε4-linked increased AD risk or enhancing the APOEε2-linked AD protection. This Review summarizes this progress and highlights areas for future research towards the development of APOE-directed therapeutics. Apolipoprotein E (APOE) is the greatest genetic modulator of sporadic Alzheimer disease risk. This Review provides a comprehensive update on our current knowledge of the genetics of APOE and its role in Alzheimer and other neurodegenerative diseases, and summarizes emerging APOE-targeted therapies designed to prevent or slow down Alzheimer disease.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":null,"pages":null},"PeriodicalIF":28.2,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141435860","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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