CAG repeat number governs the development rate of pathology in Huntington's disease

Authors

  • Dr John B. Penney Jr MD,

    Corresponding author
    1. Neurology Service, Massachusetts General Hospital, Harvard Medical School, Boston
    • Penney, Massachusetts General Hospital, Warren 408, Boston, MA 02114
    Search for more papers by this author
  • Jean-Paul Vonsattel MD,

    1. Neurology Service, Massachusetts General Hospital, Harvard Medical School, Boston
    2. Neuropathology Service, Massachusetts General Hospital, Harvard Medical School, Boston
    Search for more papers by this author
  • Marcy E. Macdonald PhD,

    1. Neurology Service, Massachusetts General Hospital, Harvard Medical School, Boston
    2. Neurogenetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston
    Search for more papers by this author
  • James F. Gusella PhD,

    1. Neurology Service, Massachusetts General Hospital, Harvard Medical School, Boston
    2. Neurogenetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston
    Search for more papers by this author
  • Richard H. Myers PhD

    1. Neurogenetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston
    2. Neurology Department, Boston University School of Medicine, Boston, MA
    Search for more papers by this author

Abstract

We compared the number of CAG repeats, the age at death, and the severity of neuropathology in 89 Huntington's disease brains. We found a linear correlation between the CAG repeat number and the quotient of the degree of atrophy in the striatum (the brain region most severely affected in Huntington's disease) divided by age at death, with an intercept at 35.5 repeats. The largest CAG repeat length, therefore, at which no pathology is expected to develop is 35.5. These results imply that striatal damage in Huntington's disease is almost entirely a lineaar function of the length of the polyglutamine stretch beyond 35.5 glutamines multiplied by the age of the patient. Thus, it is predicted that the pathological process develops linearly from birth. Analysis of other measures of striatal function could test this hypothesis and might determine when treatment for CAG repeat diseases should start.

Ancillary