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  • 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
  • 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
  • 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
  • In the first two phase II trials of therapies that target α-synuclein to treat Parkinson disease, the primary endpoints were not met. However, the limitations of these studies need to be addressed in future trials and alternative approaches to targeting α-synuclein should be pursued before α-synuclein is discounted as a target.

    • Lorraine V. Kalia
    News & Views
  • Currently, the anti-CD20 monoclonal antibody ocrelizumab is the only approved treatment for primary progressive multiple sclerosis (PPMS). However, a new study suggests that other immunomodulatory disease-modifying therapies that are often used to treat relapsing forms of multiple sclerosis could be effective in people with PPMS who have evidence of active inflammatory disease.

    • Thomas Williams
    • Jeremy Chataway
    News & Views
  • New work building on the results of genome-wide association studies in Alzheimer disease has identified molecular mechanisms that are shared with some psychiatric disorders. The study leveraged ‘omics data and has the realistic potential to elucidate unknown disease mechanisms; however, a lack of information about neuropsychiatric symptoms in the participants with Alzheimer disease limits the conclusions.

    • Byron Creese
    • Katie Lunnon
    News & Views
  • 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
  • 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
  • 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
  • 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
  • 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
  • The mechanistic contribution of cerebrovascular dysfunction to neurodegenerative diseases is difficult to determine. New single-cell transcriptomic analyses of human brain microvessels have identified transcriptomic signatures along the arteriovenous axis and transcriptional changes in the cerebrovasculature in Alzheimer disease and Huntington disease. This approach could advance our understanding of brain health and disease.

    • Masafumi Ihara
    • Yumi Yamamoto
    News & Views
  • Use of a proteomics approach has demonstrated that changes in protein expression association with Alzheimer disease are not always reflected in changes in RNA levels, highlighting the importance of directly studying proteomic changes to a full understanding of Alzheimer disease pathogenesis.

    • Marzia Perluigi
    • Eugenio Barone
    News & Views
  • A new case series describes a cohort of individuals with severe psychiatric presentations who were diagnosed with ‘possible’ or ‘probable’ autoimmune encephalitis on the basis of neurological examination. Many participants improved after treatment with immunotherapy, highlighting the importance of fostering a closer relationship between the fields of neurology and psychiatry.

    • Belinda R. Lennox
    News & Views
  • Microglia are involved in many brain disorders, yet little is known about how genetic variants impact microglial function. A new study combined genome-wide association study data with the microglial transcriptomes of the same participants to reveal functional variants underlying brain disorders. This information will help to further mechanistic studies into disease-associated microglial changes.

    • Elly M. Hol
    • R. Jeroen Pasterkamp
    News & Views
  • The largest genome-wide association study of amyotrophic lateral sclerosis to date has identified new risk loci and provided insight into factors that influence susceptibility to the disease, highlighting the possibility that disease risk and disease progression are influenced by separate factors, with therapeutic implications.

    • Tiffany W. Todd
    • Leonard Petrucelli
    News & Views
  • Two studies of the genetics of schizophrenia provide insight into somatic comorbidities and the potential of whole-genome sequencing in schizophrenia spectrum disorders, but highlight the need for more work to translate genetic findings into clinical benefits.

    • Olav B. Smeland
    • Ole A. Andreassen
    News & Views
  • Rare neurological complications can occur after COVID-19 vaccination, but recent studies show that such complications are much more common after SARS-CoV-2 infection. Novel approaches to risk–benefit analysis such as Bayesian network models can integrate the latest global evidence with local factors to inform decision-making and support the global vaccination effort.

    • Colleen L. Lau
    • Ian Galea
    News & Views