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  • Technological advances over the past decade have made precision genetic diagnosis available to many patients. The findings of a new study demonstrate that genetic diagnosis in epilepsy can lead to changes in clinical management that manifest as positive outcomes for the patient. The results herald a new era in which precision diagnosis will lead to precision medicine.

    • Katrine M. Johannesen
    News & Views
  • Here, Spires-Jones and colleagues review our current understanding of the mechanisms underlying synaptic degeneration in Alzheimer disease and highlight key questions that still need to be answered. They also discuss novel therapeutic approaches that target the synapse.

    • Makis Tzioras
    • Robert I. McGeachan
    • Tara L. Spires-Jones
    Review Article
  • Gene therapies show promise for treating epilepsy, but most strategies target cells across an entire brain region rather than selecting pathologically hyperexcited neurons. Researchers have now developed a conditional gene therapy strategy that downregulates firing activity only in neurons that are pathologically overactive and switches off when brain circuit activity has returned to baseline.

    • Pasquale Striano
    • Fabio Benfenati
    News & Views
  • Amyotrophic lateral sclerosis (ALS) is a devastating, incurable disease characterized by progressive loss of upper and lower motor neurons. Here, the authors describe the current landscape of genetic therapies for ALS and discuss new opportunities for gene replacement therapy, focusing on loss-of-function mutations.

    • Ilaria Giovannelli
    • Adrian Higginbottom
    • Pamela J. Shaw
    Review Article
  • A new study used a metagenomic approach to survey the entire gut microbiome in people with Parkinson disease and identified specific changes that could be linked to the pathogenesis of the disease.

    • Heather Wood
    Research Highlight
  • A new study provides evidence for an association between COVID-19 and long-term neurological syndromes. The findings highlight the need for further research into the long-term neurological consequences of SARS-CoV-2 infection and the development of strategies that lessen the effects of these consequences on patient quality of life and on healthcare systems.

    • Alessandro Padovani
    • Andrea Pilotto
    News & Views
  • Despite substantial research advances, treatment of neuropathic pain remains inadequate and responses to treatment are highly variable. In this Perspective, the authors argue that rational stratification of patients with neuropathic pain will aid identification of subgroups of patients who will benefit most from a given treatment.

    • Ralf Baron
    • Anthony H. Dickenson
    • David L. Bennett
    Perspective
  • In this Review, Savitz and Cox consider the evidence for a model of cell-based therapy referred to as the bioreactor hypothesis, in which exogenous cells migrate to peripheral organs and reprogramme host immune cells to generate an anti-inflammatory, regenerative environment.

    • Sean I. Savitz
    • Charles S. Cox Jr
    Review Article
  • In a study of 17,000 Medicare beneficiaries with mild cognitive impairment or dementia, non-Hispanic white older adults were more likely than Asian, Black or Hispanic older adults to have elevated cortical amyloid, as measured by PET. These findings have important implications for the use of amyloid-targeting therapies.

    • Heather E. Dark
    • Keenan A. Walker
    News & Views
  • In this Review, the authors provide an overview of evidence that activity-regulated myelination is required for brain adaptation and learning, and discuss how dysregulation of activity-dependent myelination contributes to neurological disease and could be a new therapeutic target.

    • Juliet K. Knowles
    • Ankita Batra
    • Michelle Monje
    Review Article
  • Here, the authors discuss the potential effects of social determinants of health on multiple sclerosis risk and outcomes. They suggest that addressing these determinants of health could substantially improve the lives of individuals with multiple sclerosis and call for more research.

    • Ruth Dobson
    • Dylan R. Rice
    • Helen L. Ford
    Review Article
  • Genome-wide association studies have identified loci associated with neurodegenerative disease risk, but many of the implicated genetic variants are noncoding and their functional roles remain unclear. Using massively parallel reporter assays, CRISPR-based validation and genomic annotations, a new study functionally characterizes regulatory risk variants associated with Alzheimer disease and progressive supranuclear palsy.

    • Stephanie R. Oatman
    • Nilüfer Ertekin-Taner
    News & Views