Reviews & Analysis

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  • A phase II trial of the tau antibody semorinemab indicates that it has no clinical benefit in the earliest stages of Alzheimer disease. The repeated finding that antibody-mediated reductions in protein pathology have limited or no clinical benefit indicates that we need to consider more specific or combined therapeutic targets.

    • Francesco Panza
    • Madia Lozupone
    News & Views
  • In this Review, the authors provide detailed insight into how the gut microbiota influences the immune system, with implications for neuroinflammation, and discuss the accumulating evidence that the gut microbiota is an important factor in multiple sclerosis pathogenesis and a potential therapeutic target.

    • Jorge Correale
    • Reinhard Hohlfeld
    • Sergio E. Baranzini
    Review Article
  • Cognitive rehabilitation is a promising approach to limit the effect of cognitive impairment on patients with multiple sclerosis, although results so far are conflicting. A new study indicates that structural and functional MRI techniques could provide reliable measures to predict treatment responses and tailor the rehabilitative approach to each patient.

    • Massimo Filippi
    • Paolo Preziosa
    News & Views
  • This Review considers how variants in genes encoding proteins that regulate epigenetic mechanisms might contribute to epilepsy. The discussion is structured around five categories of epigenetic mechanisms: DNA methylation, histone modifications, histone–DNA crosstalk, non-coding RNAs and chromatin remodelling.

    • Karen M. J. Van Loo
    • Gemma L. Carvill
    • David C. Henshall
    Review Article
  • In this Roadmap, Marrie and colleagues set out the steps needed to improve our understanding of the multiple sclerosis (MS) prodrome and develop standardized criteria for identifying individuals with prodromal MS, thereby facilitating trials of interventions that could slow progression to classical MS.

    • Ruth Ann Marrie
    • Mark Allegretta
    • Helen Tremlett
  • A new longitudinal study involving carriers of amyotrophic lateral sclerosis (ALS)-associated mutations has identified a prodromal phase of ALS characterized by mild motor impairment. The findings could help us to define a time window during which neuroprotective interventions might be effective in patients with genetic forms of ALS.

    • Mamede de Carvalho
    News & Views
  • The prominence of gastrointestinal dysfunction among the non-motor features of Parkinson disease (PD) indicates a close bidirectional link between the brain and the gut. This Review discusses the proposed roles of gut-related factors in PD development, progression and treatment responses, and as therapeutic targets.

    • Ai Huey Tan
    • Shen Yang Lim
    • Anthony E. Lang
    Review Article
  • In this Review, Oh and Bar-Or provide an overview of selected emerging therapies for multiple sclerosis with the potential to limit non-relapsing, progressive disease injury and to promote tissue repair, thereby addressing crucial unmet therapeutic needs.

    • Jiwon Oh
    • Amit Bar-Or
    Review Article
  • In this Perspective, the authors present their vision for a closed-loop system for automatic symptom monitoring and levodopa administration in individuals with Parkinson disease. The system would capitalize on the ongoing advances in wearable sensor technology, drug delivery systems and machine learning.

    • Hazhir Teymourian
    • Farshad Tehrani
    • Joseph Wang
  • A new genome-wide association study has identified 41 previously unknown loci associated with Alzheimer disease. However, these data provide limited insight into disease mechanisms or benefits for clinical prediction of Alzheimer disease.

    • Christina M. Lill
    • Lars Bertram
    News & Views
  • A new paper published in Neuron presents an analysis of mRNA expression in human and mouse trigeminal ganglia at single-nucleus resolution. The resulting resource is thought-provoking and suggests new targets for pain therapies; however, the findings should be interpreted in the context of the available protein data and warrant functional verification.

    • Lars Edvinsson
    • Jacob C. A. Edvinsson
    • Kristian A. Haanes
    News & Views
  • Recent technological advances have enabled the detection of specific forms of phosphorylated tau in blood. Here, the authors summarize the performance of blood phosphorylated tau biomarkers in the context of Alzheimer disease and highlight related ethical, analytical and clinical challenges.

    • Thomas K. Karikari
    • Nicholas J. Ashton
    • Henrik Zetterberg
    Review Article
  • Many episodes of status epilepticus do not respond to first-line treatment with benzodiazepines. In this Perspective, Richard Burman and colleagues discuss seizure-induced alterations to the sensitivity of the GABA receptor to benzodiazepines, presenting these changes as a possible mechanism of treatment resistance.

    • Richard J. Burman
    • Richard E. Rosch
    • Joseph V. Raimondo
  • In this Review, Diener et al. discuss the concept of embolic stroke of undetermined source, proposing updates to the criteria and diagnostic algorithm in light of evidence gathered since the concept was first introduced.

    • Hans-Christoph Diener
    • J. Donald Easton
    • George Ntaios
    Review Article
  • The term ‘rapidly progressive dementia’ (RPD) describes a cognitive disorder with fast progression, leading to dementia within a relatively short time. This Review discusses the wide range of RPD aetiologies, as well as the diagnostic approach and treatment options.

    • Peter Hermann
    • Inga Zerr
    Review Article
  • In this Review, Coyne and Rothstein discuss disruptions to the nuclear pore complex and nucleocytoplasmic transport, which are emerging as pathological mechanisms in multiple neurodegenerative diseases, and consider the effects of these changes on cellular function and their potential for therapeutic targeting.

    • Alyssa N. Coyne
    • Jeffrey D. Rothstein
    Review Article
  • Analysis of brain images taken before and after infection with SARS-CoV-2 suggests that even mild COVID-19 is associated with brain structure alterations and cognitive impairment. However, the clinical implications for individuals are unclear and further studies are needed to assess the generalizability of the findings and whether the effects are long-lasting.

    • Stéphane Kremer
    • H. Rolf Jäger
    News & Views
  • A recent publication reveals progressive, dose-dependent ventricular enlargement in the brains of patients with early Alzheimer disease who were treated with the FDA-approved drug aducanumab. Aducanumab joins a growing list of anti-amyloid-β therapies for which there is evidence that they cause accelerated neurodegeneration; extended follow-up studies are required to determine whether aducanumab causes progressive brain damage.

    • Scott Ayton
    News & Views
  • In this Review, the authors discuss how various immunotherapies for neuroimmunological diseases interact with vaccination responses, including responses to SARS-CoV-2 vaccinations, and the implications for the safe and effective use of vaccines in patients with these diseases.

    • Alexander Winkelmann
    • Micha Loebermann
    • Uwe K. Zettl
    Review Article