Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations.

Multiple sclerosis (MS) is a neuro-inflammatory and neurodegenerative disease that is most prevalent in Northern Europe. Although it is known that inherited risk for MS is located within or in close proximity to immune-related genes, it is unknown when, where and how this genetic risk originated1. Here, by using a large ancient genome dataset from the Mesolithic period to the Bronze Age2, along with new Medieval and post-Medieval genomes, we show that the genetic risk for MS rose among pastoralists from the Pontic steppe and was brought into Europe by the Yamnaya-related migration approximately 5,000 years ago. We further show that these MS-associated immunogenetic variants underwent positive selection both within the steppe population and later in Europe, probably driven by pathogenic challenges coinciding with changes in diet, lifestyle and population density. This study highlights the critical importance of the Neolithic period and Bronze Age as determinants of modern immune responses and their subsequent effect on the risk of developing MS in a changing environment.

The Gray Degeneration of the Brain and Spinal Cord: A Story of the Once Favored Diagnosis With Subsequent Vessel-Based Etiopathological Studies in Multiple Sclerosis.

In 1857, French-Austrian psychiatrist Bénédict Augustin Morel (1809-1873) published his infamous though highly successful Traité des dégénérescences physiques, intellectuelles et morales de l'espèce humaine, which was fully dedicated to the social problem of "degeneration" and its psychiatric and neurological underpinnings. European psychiatrists, neurologists, and pathologists integrated Morel's approach into their neuropsychiatric theories and searched for the somatic and morphological alterations in the human brain, as did the versatile pupil of Rudolph Virchow (1821-1902), Georg Eduard von Rindfleisch (1836-1908), in his Lehrbuch der pathologischen Gewebelehre (1867). This can be seen as a starting point of research into the vascular genesis of "multiple sclerosis" by observing that the changes of blood vessels and nerve elements could be the result of inflammation and increased blood flow. We examine the waxing and waning of a 19th century diagnostic condition, which fell out of favor and resurfaced during the 20th century.

Tatsushi Igaki: Flying up the research summits.

Igaki explores how cell-cell communication directs tissue and tumor development.

Dale Schenk One Year Anniversary: Fighting to Preserve the Memories.

It has been a year since we lost Dale Schenk on September 30, 2016. Dale's visionary work resulted in the remarkable discovery in 1999 that an experimental amyloid-ß (Aß) vaccine reduced the neurodegeneration in a transgenic model of Alzheimer's disease (AD). Following Dale's seminal work, several active and passive immunotherapies have since been developed and tested in the clinic for AD, Parkinson's disease (PD), and other neurodegenerative disorders. Here we provide a brief overview of the current state of development of immunotherapy for AD, PD, and other neurodegenerative disorders in the context of this anniversary. The next steps in the development of immunotherapies will require combinatorial approaches mixing antibodies against various targets (e.g., Aß, α-syn, Tau, and TDP43) with small molecules that block toxicity, aggregation, inflammation, and promote cell survival.

Untangling the tauopathies: Current concepts of tau pathology and neurodegeneration.

Tau is the most common misfolded protein responsible for human neurodegenerative diseases. The identification of mutations in MAPT, the gene that encodes tau, causing dementia and parkinsonism established the notion that tau aggregation is responsible for the development of disease. An increased understanding of the pathway leading from conformational changes in tau protein and tau propagation to neuronal dysfunction, cell death and clinical manifestation will be the key for the development mechanism-based therapeutic strategies for tauopathies.

Corticobasal degeneration: key emerging issues.

Corticobasal degeneration (CBD) was first described by Rebeiz et al. in 1967, and was called corticodentatonigral degeneration with neuronal achromasia [1]. Since then, our knowledge of the clinical features and underlying tau pathology has grown tremendously. Clinical antemortem diagnosis of CBD pathology remains challenging and has led to the development of revised diagnostic criteria. As various clinical phenotypes may have CBD pathology, accurate prevalence studies are lacking. Recently, pooled prevalence of fronto-temporal lobar degeneration, PSP and CBS was reported as 10.6 per 100,000 [2]. Although rare, CBD is an important disease to understand because it provides a model of a specific proteinopathy (tauopathy) and, therefore, opportunity to study pathophysiology of tauopathies and efficacy of tau-directed therapies. In the past few years, identification of tau specific ligands has advanced neuroimaging of tauopathies such as CBD and progressive supranuclear palsy. However, clinical prediction of CBD pathology remains challenging and an active are of research. In this review, we highlight key emerging issues in CBD pathophysiology, genetics and novel neuroimaging techniques with tau ligands.

John Hardy is the UK's first Breakthrough Prize laureate.

John Hardy, Professor of Neuroscience at University College London and Editorial Board member of The FEBS Journal, has been awarded The Breakthrough Prize in Life Sciences in recognition of his work identifying mutations that cause amyloid build-up in the brain--research that has transformed the study of Alzheimer's disease and other major neurodegenerative diseases.

Chronic traumatic encephalopathy in professional sports: retrospective and prospective views.

PRIMARY OBJECTIVE: The purposes of this paper are to review: (1) the history of chronic traumatic encephalopathy (CTE) in sports, (2) the similarities and differences between historic and current definitions of CTE, (3) recent epidemiology and cohort studies of CTE and (4) controversies regarding the current CTE positions. RESEARCH DESIGN: Not applicable. METHODS AND PROCEDURES: Selective review of published articles relevant to CTE. MAIN OUTCOME AND RESULTS: The current definitions of CTE have evolved from its original definition and now rely heavily on the post-mortem detection of hyperphosphorylated tau for diagnosis. As of 2013, there is a blended cohort of 110 professional athletes diagnosed with CTE. It is being assumed that concussions and/or sub-concussive impacts in contact sports are the sole cause of CTE. CONCLUSIONS: There are multiple causes of abnormal tau protein deposition in the human brain and the pathogenesis of CTE may not be related solely to concussion and/or sub-concussive injury. In all likelihood, the causes of CTE are a multivariate, as opposed to a univariate, phenomenon.

A short history of the notion of neurodegenerative disease.

The notion of heredity of degenerative constitutions of human beings contributed in the nineteenth century to the fear for deterioration of the human race and in the twentieth century to attempts by several Western Countries, particularly Germany, to improve the inborn qualities of their populations by eugenic measures. In the years following World War II, the term eugenics was eradicated from medicine. The qualification degenerative disappeared from genetics and psychiatry but remained in use to denote decay of tissues and cells. The adjective neurodegenerative came in vogue in neurology and was mostly applied to brain diseases. Definitions in the literature indicate that neurodegenerative diseases are considered as to be age related, incurable, and largely untreatable chronic progressive diseases of the central nervous system. Scrutiny of available data shows that the notion concerns an ill-defined group of genetic and idiopathic disorders. Genetic central nervous system diseases may become manifest at all ages and are accessible for symptomatic treatment. Investigations of animal models suggest that not all neurodegenerative diseases are inherently incurable. Alternatives for the terms neurodegenerative and degenerative are available.

[Dualism and malaise in psychiatry]. / Dualisme et malaise dans la psychiatrie.

The history of psychiatry is characterised by the confrontation of theoretical models, or dualism.The contrast between these trends has always added to the richness of this discipline, from Philippe Pinel to Henri Ey, and from Bénédict-Augustin Morel to Valentin Magnan.Today, we are faced with an epistemological malaise which is the result of the domination of neurosciences. In order to protect against the temptation to allow the domination of one of the theoretical models, a return to dualism is recommended.