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

JB Penney Jr, JP Vonsattel… - Annals of Neurology …, 1997 - Wiley Online Library
JB Penney Jr, JP Vonsattel, ME Macdonald, JF Gusella, RH Myers
Annals of Neurology: Official Journal of the American Neurological …, 1997Wiley Online Library
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 …
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.
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