CAG repeat number governs the development rate of pathology in Huntington's disease.
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 linear 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.
Penney
J B
JB
Neurology Service, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Vonsattel
J P
JP
MacDonald
M E
ME
Gusella
J F
JF
Myers
R H
RH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy; D001921:Brain / Q000473:pathology; D006801:Humans; D006816:Huntington Disease / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D016019:Survival Analysis; D018911:Trinucleotide Repeats