Reviews & Analysis

In this Review, the authors describe the current data detailing the role of triggering receptor expressed on myeloid cells (TREM2) in microglial biology and Alzheimer disease (AD), and discuss the possibility of targeting TREM2 as a treatment for AD.

A new study has shown that peritoneal dialysis and isochronic parabiosis can clear misfolded tau proteins from mouse brain. The findings add to our understanding of how Alzheimer disease-associated proteins can be therapeutically removed by peripheral interventions.

A new publication from the Whitehall study confirms earlier findings that light to moderate alcohol drinkers have a reduced risk of dementia compared with abstainers and heavy drinkers. Importantly, the study follows a cohort from middle age, whereas most previous research on this topic has focused on older adults.

In this Review, Khalil et al. consider how technological advances have enabled the detection of neurofilament proteins in the blood, and discuss how these proteins consequently have the potential to be easily measured biomarkers of neuroaxonal injury in various neurological conditions.

During cluster headache attacks, plasma levels of calcitonin gene-related peptide (CGRP) increase, and trigeminal nerve activation leads to pain. A new study shows that CGRP infusion can induce cluster headache attacks in some patients, with important implications for the investigation of CGRP-targeted therapies in cluster headache.

Lafora disease is an autosomal recessive, progressive myoclonus epilepsy caused by loss of function of laforin or malin, leading to impaired glycogen metabolism. The authors review the clinical and molecular features of Lafora disease and discuss current and emerging treatment options.

In this Review, the authors consider advances over the past decade that have set the stage for a resurgence in attempts to predict seizures in epilepsy, and they propose new avenues of investigation that combine mechanisms, models, data, devices and algorithms.

Advances in our understanding of the pathogenic mechanisms of spinocerebellar ataxias (SCAs) have resulted in the development of promising therapeutic strategies for these inherited neurodegenerative disorders. Here, Ashizawa and colleagues review the current progress and future challenges facing clinical trials of new therapies for the SCAs.

Repeat expansions in the C9orf72 gene are a frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Balendra and Isaacs review the pathological and mechanistic features of C9orf72-associated ALS and FTD, highlighting loss-of-function, gain-of-function and downstream mechanisms.

Multimodal imaging in neurodegenerative disorders can provide insights on structural, functional and neurochemical alterations that might not be possible via clinical testing alone. New findings on multimodal imaging in idiopathic REM sleep behaviour disorder (iRBD) have implications for the relationship between iRBD, the clinical phenotype of Parkinson disease and the underlying substrate of Lewy body disease, particularly for understanding the pathophysiology and designing disease-modifying therapies.

In this Review, the authors consider the evidence for the contribution of various factors to the pathogenesis of cerebral palsy, highlighting the complexities in its aetiology to inform translational research for the prevention of cerebral palsy.

Patent foramen ovale (PFO) is prevalent among young patients with cryptogenic stroke, and PFO closure reduces the risk of recurrent stroke in these individuals. A new study confirms that PFO is also frequent in patients with cryptogenic stroke aged >60 years, but the optimal management of such patients remains unresolved.

Migraine is prevalent in the paediatric population and represents a major cause of disability. This Review outlines the epidemiology and natural history of paediatric migraine, discusses the recent landmark clinical trials of treatments for paediatric migraine and examines the best evidence-based interventions for this population in light of these new findings.

In a recent study, rivaroxaban was not superior to aspirin for secondary prevention of stroke and systemic emboli after an initial embolic stroke of undetermined source (ESUS) but was associated with a higher risk of bleeding. What does that mean for the concept of ESUS and for future trials?

Moderate and severe traumatic brain injuries (TBIs) have long been recognized as risk factors for dementia, but the relationship between mild TBI (mTBI) and dementia is unclear. New research demonstrates that even an mTBI without loss of consciousness is associated with a twofold increase in the risk of dementia.

Glioblastomas remain one of the most aggressive and lethal tumours, with no effective treatments available. Here, Xandra Breakefield and colleagues examine the ways in which glioblastomas manipulate brain cells and immune cells in their environment to support tumour growth and the opportunities available for new therapies that disrupt these interactions.

In this Review, Ferretti et al. discuss the evidence for sex-related differences in Alzheimer disease symptoms, progression, risk factors and treatment, and consider how understanding sex differences is crucial in developing precision medicine.

This Review appraises the available evidence for spatial navigation and/or orientation deficits in preclinical, prodromal and confirmed Alzheimer disease with a focus on using spatial navigation as a diagnostic tool. Research gaps and future research priorities are also identified.

Eteplirsen, a compound designed to restore dystrophin in patients with Duchenne muscular dystrophy, controversially received approval by the FDA in 2016. Owing to limited clinical data, the approval was based on eteplirsen’s effect on dystrophin expression. Now, the dystrophin quantification results have been published, and although low levels of dystrophin expression are shown, the quantification remains debatable.

Non-rapid eye movement (NREM) sleep parasomnias are thought to derive from incomplete arousal from NREM sleep. Here, the authors present evidence for coexistence of sleep-like and wake-like brain activity in disorders of arousal, including confusional arousals, sleep terrors and sleepwalking.