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
{"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}
Michael Benatar, Joanne Wuu, Edward D. Huey, Corey T. McMillan, Ronald C. Petersen, Ronald Postuma, Caroline McHutchison, Laynie Dratch, Jalayne J. Arias, Anita Crawley, Henry Houlden, Michael P. McDermott, Xueya Cai, Neil Thakur, Adam Boxer, Howard Rosen, Bradley F. Boeve, Penny Dacks, Stephanie Cosentino, Sharon Abrahams, Neil Shneider, Paul Lingor, Jeremy Shefner, Peter M. Andersen, Ammar Al-Chalabi, Martin R. Turner, Attendees of the Second International Pre-Symptomatic ALS Workshop
{"title":"Publisher Correction: The Miami Framework for ALS and related neurodegenerative disorders: an integrated view of phenotype and biology","authors":"Michael Benatar, Joanne Wuu, Edward D. Huey, Corey T. McMillan, Ronald C. Petersen, Ronald Postuma, Caroline McHutchison, Laynie Dratch, Jalayne J. Arias, Anita Crawley, Henry Houlden, Michael P. McDermott, Xueya Cai, Neil Thakur, Adam Boxer, Howard Rosen, Bradley F. Boeve, Penny Dacks, Stephanie Cosentino, Sharon Abrahams, Neil Shneider, Paul Lingor, Jeremy Shefner, Peter M. Andersen, Ammar Al-Chalabi, Martin R. Turner, Attendees of the Second International Pre-Symptomatic ALS Workshop","doi":"10.1038/s41582-024-00978-4","DOIUrl":"10.1038/s41582-024-00978-4","url":null,"abstract":"","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":null,"pages":null},"PeriodicalIF":38.1,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41582-024-00978-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174324","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}
Sebastian Ocklenburg, Annakarina Mundorf, Robin Gerrits, Emma M. Karlsson, Marietta Papadatou-Pastou, Guy Vingerhoets
{"title":"Clinical implications of brain asymmetries","authors":"Sebastian Ocklenburg, Annakarina Mundorf, Robin Gerrits, Emma M. Karlsson, Marietta Papadatou-Pastou, Guy Vingerhoets","doi":"10.1038/s41582-024-00974-8","DOIUrl":"10.1038/s41582-024-00974-8","url":null,"abstract":"No two human brains are alike, and with the rise of precision medicine in neurology, we are seeing an increased emphasis on understanding the individual variability in brain structure and function that renders every brain unique. Functional and structural brain asymmetries are a fundamental principle of brain organization, and recent research suggests substantial individual variability in these asymmetries that needs to be considered in clinical practice. In this Review, we provide an overview of brain asymmetries, variations in such asymmetries and their relevance in the clinical context. We review recent findings on brain asymmetries in neuropsychiatric and neurodevelopmental disorders, as well as in specific learning disabilities, with an emphasis on large-scale database studies and meta-analyses. We also highlight the relevance of asymmetries for disease symptom onset in neurodegenerative diseases and their implications for lateralized treatments, including brain stimulation. We conclude that alterations in brain asymmetry are not sufficiently specific to act as diagnostic biomarkers but can serve as meaningful symptom or treatment response biomarkers in certain contexts. On the basis of these insights, we provide several recommendations for neurological clinical practice. Functional and structural brain asymmetries are a fundamental principle of brain organization, and research suggests substantial individual variability in these asymmetries that needs to be considered in clinical practice. This Review provides an overview of brain asymmetries, variations in such asymmetries and their relevance in the context of clinical neurology.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":null,"pages":null},"PeriodicalIF":28.2,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141085187","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}
Michael Benatar, Joanne Wuu, Edward D. Huey, Corey T. McMillan, Ronald C. Petersen, Ronald Postuma, Caroline McHutchison, Laynie Dratch, Jalayne J. Arias, Anita Crawley, Henry Houlden, Michael P. McDermott, Xueya Cai, Neil Thakur, Adam Boxer, Howard Rosen, Bradley F. Boeve, Penny Dacks, Stephanie Cosentino, Sharon Abrahams, Neil Shneider, Paul Lingor, Jeremy Shefner, Peter M. Andersen, Ammar Al-Chalabi, Martin R. Turner, Attendees of the Second International Pre-Symptomatic ALS Workshop
{"title":"The Miami Framework for ALS and related neurodegenerative disorders: an integrated view of phenotype and biology","authors":"Michael Benatar, Joanne Wuu, Edward D. Huey, Corey T. McMillan, Ronald C. Petersen, Ronald Postuma, Caroline McHutchison, Laynie Dratch, Jalayne J. Arias, Anita Crawley, Henry Houlden, Michael P. McDermott, Xueya Cai, Neil Thakur, Adam Boxer, Howard Rosen, Bradley F. Boeve, Penny Dacks, Stephanie Cosentino, Sharon Abrahams, Neil Shneider, Paul Lingor, Jeremy Shefner, Peter M. Andersen, Ammar Al-Chalabi, Martin R. Turner, Attendees of the Second International Pre-Symptomatic ALS Workshop","doi":"10.1038/s41582-024-00961-z","DOIUrl":"10.1038/s41582-024-00961-z","url":null,"abstract":"Increasing appreciation of the phenotypic and biological overlap between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, alongside evolving biomarker evidence for a pre-symptomatic stage of disease and observations that this stage of disease might not always be clinically silent, is challenging traditional views of these disorders. These advances have highlighted the need to adapt ingrained notions of these clinical syndromes to include both the full phenotypic continuum — from clinically silent, to prodromal, to clinically manifest — and the expanded phenotypic spectrum that includes ALS, frontotemporal dementia and some movement disorders. The updated clinical paradigms should also align with our understanding of the biology of these disorders, reflected in measurable biomarkers. The Miami Framework, emerging from discussions at the Second International Pre-Symptomatic ALS Workshop in Miami (February 2023; a full list of attendees and their affiliations appears in the Supplementary Information) proposes a classification system built on: first, three parallel phenotypic axes — motor neuron, frontotemporal and extrapyramidal — rather than the unitary approach of combining all phenotypic elements into a single clinical entity; and second, biomarkers that reflect different aspects of the underlying pathology and biology of neurodegeneration. This framework decouples clinical syndromes from biomarker evidence of disease and builds on experiences from other neurodegenerative diseases to offer a unified approach to specifying the pleiotropic clinical manifestations of disease and describing the trajectory of emergent biomarkers. In this Perspective, the authors propose a new classification system for amyotrophic lateral sclerosis and related neurodegenerative disorders that recognizes, in parallel, the clinical syndromes and the underlying biology of disease. The framework emerged from discussions at the Second International Pre-Symptomatic ALS Workshop in Miami (February 2023).","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":null,"pages":null},"PeriodicalIF":38.1,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141069436","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}