Preventing amyotrophic lateral sclerosis: insights from pre-symptomatic neurodegenerative diseases

作者：Michael Benatar, Joanne Wuu, Caroline McHutchison, Ronald B. Postuma, Bradley F. Boeve, Ronald C. Petersen, Christopher A. Ross, Howard J. Rosen, Jalayne J. Arias, Stephanie Fradette, Michael McDermott, Jeremy M. Shefner, Christine Stanislaw, Sharon Abrahams, Stephanie Cosentino, Peter M Andersen, Richard S. Finkel, Volkan Granit, Anne‐Laure Grignon, Jonathan D. Rohrer, Corey T. McMillan, Murray Grossman, Ammar Al-Chalabi, Martin R. Turner, First International Pre-Symptomatic ALS Workshop, Ammar Al-Chalabi, Peter M Andersen, Jalayne J. Arias, Michael Benatar, Bradley F. Boeve, Stephanie Cosentino, Kuldip D. Dave, Toby A. Ferguson, Mary-Kay Floeter, Jonathan D. Rohrer, Stephanie Fradette, Tania F. Gendron, Volkan Granit, Anne‐Laure Grignon, Murray Grossman, Amelie K. Gubitz, Petra Kaufman, Isabelle Le Ber, Suzee Lee, Andrea Malaspina, Michael McDermott, Caroline McHutchison, Corey T. McMillan, Katie Nicholson, Ronald C. Petersen, Ronald B. Postuma, Richard Robinson, Howard J. Rosen, Christopher A. Ross, Jeremy M. Shefner, Christine Stanislaw, Nadine Tatton, Neil Thakur, Martin R. Turner, Jochen H. Weishaupt, Joanne Wuu · 发表于：Brain · 年份：2021 · DOI：10.1093/brain/awab404 · 被引用次数：125 · 研究领域：Amyotrophic Lateral Sclerosis Research、Parkinson's Disease Mechanisms and Treatments、Neurogenetic and Muscular Disorders Research

Significant progress has been made in understanding the pre-symptomatic phase of amyotrophic lateral sclerosis. While much is still unknown, advances in other neurodegenerative diseases offer valuable insights. Indeed, it is increasingly clear that the well-recognized clinical syndromes of Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal muscular atrophy and frontotemporal dementia are also each preceded by a pre-symptomatic or prodromal period of varying duration, during which the underlying disease process unfolds, with associated compensatory changes and loss of inherent system redundancy. Key insights from these diseases highlight opportunities for discovery in amyotrophic lateral sclerosis. The development of biomarkers reflecting amyloid and tau has led to a shift in defining Alzheimer's disease based on inferred underlying histopathology. Parkinson's disease is unique among neurodegenerative diseases in the number and diversity of non-genetic biomarkers of pre-symptomatic disease, most notably REM sleep behaviour disorder. Huntington's disease benefits from an ability to predict the likely timing of clinically manifest disease based on age and CAG-repeat length alongside reliable neuroimaging markers of atrophy. Spinal muscular atrophy clinical trials have highlighted the transformational value of early therapeutic intervention, and studies in frontotemporal dementia illustrate the differential role of biomarkers based on genotype. Similar advance...