Nature Reviews Neurology最新文献

{"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":"20 8","pages":"457-474"},"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}

{"title":"Neurology under the midnight sun: EAN Congress 2024 comes to Helsinki","authors":"Heather Wood","doi":"10.1038/s41582-024-00982-8","DOIUrl":"10.1038/s41582-024-00982-8","url":null,"abstract":"The 10th Congress of the European Academy of Neurology is being held in Helsinki, Finland from 29 June to 2 July 2024, and Nature Reviews Neurology is publishing a series of Comments on the overarching theme, neuromodulation. We asked Programme Committee Chairs Ulf Kallweit and Reetta Kälviäinen about their roles and their expectations for the congress.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 8","pages":"453-454"},"PeriodicalIF":28.2,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432306","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":"From spreading depolarization to blood–brain barrier dysfunction: navigating traumatic brain injury for novel diagnosis and therapy","authors":"Gerben van Hameren, Refat Aboghazleh, Ellen Parker, Jens P. Dreier, Daniela Kaufer, Alon Friedman","doi":"10.1038/s41582-024-00973-9","DOIUrl":"10.1038/s41582-024-00973-9","url":null,"abstract":"Considerable strides in medical interventions during the acute phase of traumatic brain injury (TBI) have brought improved overall survival rates. However, following TBI, people often face ongoing, persistent and debilitating long-term complications. Here, we review the recent literature to propose possible mechanisms that lead from TBI to long-term complications, focusing particularly on the involvement of a compromised blood–brain barrier (BBB). We discuss evidence for the role of spreading depolarization as a key pathological mechanism associated with microvascular dysfunction and the transformation of astrocytes to an inflammatory phenotype. Finally, we summarize new predictive and diagnostic biomarkers and explore potential therapeutic targets for treating long-term complications of TBI. Overall survival rates for traumatic brain injury have improved, but affected individuals often experience persistent and debilitating long-term complications. In this Review, the authors discuss recent evidence for the role of spreading depolarization in the initiation of long-term pathology in traumatic brain injury, including effects on blood–brain barrier dysfunction and neuroinflammation.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 7","pages":"408-425"},"PeriodicalIF":28.2,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141333717","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":"Acceptable performance of blood biomarker tests of amyloid pathology — recommendations from the Global CEO Initiative on Alzheimer’s Disease","authors":"Suzanne E. Schindler, Douglas Galasko, Ana C. Pereira, Gil D. Rabinovici, Stephen Salloway, Marc Suárez-Calvet, Ara S. Khachaturian, Michelle M. Mielke, Chi Udeh-Momoh, Joan Weiss, Richard Batrla, Sasha Bozeat, John R. Dwyer, Drew Holzapfel, Daryl Rhys Jones, James F. Murray, Katherine A. Partrick, Emily Scholler, George Vradenburg, Dylan Young, Alicia Algeciras-Schimnich, Jiri Aubrecht, Joel B. Braunstein, James Hendrix, Yan Helen Hu, Soeren Mattke, Mark Monane, David Reilly, Elizabeth Somers, Charlotte E. Teunissen, Eli Shobin, Hugo Vanderstichele, Michael W. Weiner, David Wilson, Oskar Hansson","doi":"10.1038/s41582-024-00977-5","DOIUrl":"10.1038/s41582-024-00977-5","url":null,"abstract":"Anti-amyloid treatments for early symptomatic Alzheimer disease have recently become clinically available in some countries, which has greatly increased the need for biomarker confirmation of amyloid pathology. Blood biomarker (BBM) tests for amyloid pathology are more acceptable, accessible and scalable than amyloid PET or cerebrospinal fluid (CSF) tests, but have highly variable levels of performance. The Global CEO Initiative on Alzheimer’s Disease convened a BBM Workgroup to consider the minimum acceptable performance of BBM tests for clinical use. Amyloid PET status was identified as the reference standard. For use as a triaging test before subsequent confirmatory tests such as amyloid PET or CSF tests, the BBM Workgroup recommends that a BBM test has a sensitivity of ≥90% with a specificity of ≥85% in primary care and ≥75–85% in secondary care depending on the availability of follow-up testing. For use as a confirmatory test without follow-up tests, a BBM test should have performance equivalent to that of CSF tests — a sensitivity and specificity of ~90%. Importantly, the predictive values of all biomarker tests vary according to the pre-test probability of amyloid pathology and must be interpreted in the complete clinical context. Use of BBM tests that meet these performance standards could enable more people to receive an accurate and timely Alzheimer disease diagnosis and potentially benefit from new treatments. Anti-amyloid treatments for early symptomatic Alzheimer disease have greatly increased the need for biomarker confirmation of amyloid pathology and blood biomarker tests offer an accessible and scalable biomarker test. This Consensus Statement provides recommendations for the minimum acceptable performance of blood biomarker tests for clinical use.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 7","pages":"426-439"},"PeriodicalIF":28.2,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41582-024-00977-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309022","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}

{"title":"Alzheimer disease blood biomarkers: considerations for population-level use","authors":"Michelle M. Mielke, Nicole R. Fowler","doi":"10.1038/s41582-024-00989-1","DOIUrl":"10.1038/s41582-024-00989-1","url":null,"abstract":"In the past 5 years, we have witnessed the first approved Alzheimer disease (AD) disease-modifying therapy and the development of blood-based biomarkers (BBMs) to aid the diagnosis of AD. For many reasons, including accessibility, invasiveness and cost, BBMs are more acceptable and feasible for patients than a lumbar puncture (for cerebrospinal fluid collection) or neuroimaging. However, many questions remain regarding how best to utilize BBMs at the population level. In this Review, we outline the factors that warrant consideration for the widespread implementation and interpretation of AD BBMs. To set the scene, we review the current use of biomarkers, including BBMs, in AD. We go on to describe the characteristics of typical patients with cognitive impairment in primary care, who often differ from the patient populations used in AD BBM research studies. We also consider factors that might affect the interpretation of BBM tests, such as comorbidities, sex and race or ethnicity. We conclude by discussing broader issues such as ethics, patient and provider preference, incidental findings and dealing with indeterminate results and imperfect accuracy in implementing BBMs at the population level. Blood-based biomarkers have the potential to transform the Alzheimer disease diagnostic pathway, but many questions remain regarding their implementation and utilization. This Review considers factors that might affect the interpretation of blood-based biomarker tests, including comorbidities, sex and race or ethnicity, and discusses broader issues surrounding their use at the population level.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 8","pages":"495-504"},"PeriodicalIF":28.2,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141304479","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":"Brain clearance not increased during sleep","authors":"Ian Fyfe","doi":"10.1038/s41582-024-00983-7","DOIUrl":"10.1038/s41582-024-00983-7","url":null,"abstract":"","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 7","pages":"379-379"},"PeriodicalIF":28.2,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237910","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":"Potassium regulation could be key to healthy brain ageing","authors":"Ian Fyfe","doi":"10.1038/s41582-024-00984-6","DOIUrl":"10.1038/s41582-024-00984-6","url":null,"abstract":"","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 7","pages":"379-379"},"PeriodicalIF":28.2,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237879","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":"APOE α4 homozygosity — a genetic form of Alzheimer disease?","authors":"Ian Fyfe","doi":"10.1038/s41582-024-00985-5","DOIUrl":"10.1038/s41582-024-00985-5","url":null,"abstract":"","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 7","pages":"379-379"},"PeriodicalIF":28.2,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237906","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":"Microglial senescence is a potential therapeutic target for Alzheimer disease","authors":"Heather Wood","doi":"10.1038/s41582-024-00979-3","DOIUrl":"10.1038/s41582-024-00979-3","url":null,"abstract":"A new study has identified prematurely senescent microglia in the vicinity of amyloid-β plaques in the brains of individuals with Alzheimer disease.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 7","pages":"379-379"},"PeriodicalIF":28.2,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237849","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":"Genes associated with multiple system atrophy","authors":"Ian Fyfe","doi":"10.1038/s41582-024-00986-4","DOIUrl":"10.1038/s41582-024-00986-4","url":null,"abstract":"","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 7","pages":"379-379"},"PeriodicalIF":28.2,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237914","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}