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August 14, 2012; 79 (7) Editorials

Development and neurodegeneration

Turning HD pathogenesis on its head

Karen Marder, Mark F. Mehler
First published July 18, 2012, DOI: https://doi.org/10.1212/WNL.0b013e3182648bfe
Karen Marder
From the Departments of Neurology and Psychiatry, Sergievsky Center, and Taub Institute (K.M.), College of Physicians and Surgeons, Columbia University, New York, NY; and the Institute for Brain Disorders and Neural Regeneration, Departments of Neurology, Neuroscience, and Psychiatry and Behavioral Sciences, Rose F Kennedy Center for Research on Intellectual and Developmental Disabilities, and the Einstein Cancer Center (M.F.M.), Albert Einstein College of Medicine, Bronx, NY.
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Mark F. Mehler
From the Departments of Neurology and Psychiatry, Sergievsky Center, and Taub Institute (K.M.), College of Physicians and Surgeons, Columbia University, New York, NY; and the Institute for Brain Disorders and Neural Regeneration, Departments of Neurology, Neuroscience, and Psychiatry and Behavioral Sciences, Rose F Kennedy Center for Research on Intellectual and Developmental Disabilities, and the Einstein Cancer Center (M.F.M.), Albert Einstein College of Medicine, Bronx, NY.
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Development and neurodegeneration
Turning HD pathogenesis on its head
Karen Marder, Mark F. Mehler
Neurology Aug 2012, 79 (7) 621-622; DOI: 10.1212/WNL.0b013e3182648bfe

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The term “neurodegenerative” implies a period of normal development preceding cell death. Determining when decline begins and the selective vulnerability of specific brain regions to the degenerative cascade is key to development of disease-modifying therapies. Huntington disease (HD), an autosomal dominant disease with little contribution from modifier genes, and complete penetrance in individuals with CAG repeat length ≥40 in the Huntington (Htt) gene, permits the identification of an at-risk population for whom the probability of age at diagnosis can be modeled based on CAG repeat length and age. What if Huntington disease is both a neurodevelopmental disorder and a neurodegenerative disease?

The possibility that mutant Htt (mHtt) might result in fundamental embryonic developmental abnormalities that correlate with the patterns of …

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