Volume 9 Issue 2, February 2013

In 2012, researchers published extensively on the genetic and clinicopathological characterization of patients with the newly discovered C9ORF72 repeat expansions, which cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Novel ALS-linked genes and genetic modifiers were identified through screening in animal models and patients.

In 2012, studies of autosomal dominant Alzheimer disease (AD), late-onset AD, and a rare genetic mutation of amyloid precursor protein provided support for the critical role of amyloid in AD pathogenesis. Increasing evidence implicated cell-to-cell transmission in the spread of tau and amyloid, highlighting novel targets for therapeutic intervention.

Research on epilepsies in 2012 has substantially advanced our knowledge of these often devastating conditions. From important discoveries that revealed causative factors and the molecular basis of disease, to major implications for surgical decision-making, these studies set the scene for future advances in the field.

Several clinical trials and experimental studies that could have a major impact on the treatment of patients with ischaemic stroke were published in 2012. The studies cover all therapeutic options, including stroke prevention, recanalization and thrombolysis, neuroprotection, and promising new therapeutic approaches focused on neurorepair.

Research in movement disorders in 2012 has improved our understanding of the pathogenic mechanisms of disease and led to development of potential novel therapeutic approaches. Key advances were linked to mechanisms underlying spread of neurodegenerative pathology, immunotherapy, stem cells, genetics and deep brain stimulation in parkinsonism and related disorders.

2012 witnessed important developments for multiple sclerosis, including successful phase III trials of novel oral therapeutics and identification of the potassium channel KIR4.1 as an autoimmune target. Additionally, the lung was highlighted as an important site for immune-cell programming, and the relevance of a TNF receptor variant was clarified.

Eye movement responses are altered in patients with age-related neurodegenerative diseases such as Huntington disease or Parkinson disease. In this Review, the authors describe the oculomotor features of various neurodegenerative diseases and discuss the potential utility of laboratory and clinical assessment of eye movements in monitoring of onset and progression in patients with these disorders.

Transient amnesic syndromes, such as transient global amnesia and transient epileptic amnesia, are often difficult to diagnose. Recent studies, however, have examined the structural and functional underpinnings of these disorders. In this Review, Bartsch and Butler discuss how these studies have improved our understanding of transient amnesic syndromes, summarizing the key clinical aspects of different amnesic disorders and providing recommendations for diagnosis and patient management.

Prion diseases are a group of fatal neurodegenerative disorders caused by accumulation of misfolded prion protein. The time from infection to onset of disease symptoms can be decades, and the public health risk from infective prions is considerable. In this Review the authors discuss current research into passive and active immunization strategies against prion diseases, and the potential for effective therapy.

The ε4 allele of the apolipoprotein E (APOE) gene is the strongest genetic risk factor for Alzheimer disease (AD). Guojun Bu and colleagues describe the pathogenic links between Apo-E4 and neurodegeneration, including amyloid-β-dependent mechanisms and impairment of neurovascular function. The authors suggest potential strategies to target Apo-E, which could provide important additions to therapeutic options for AD.