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Relationship between trinucliotide repeats and neuropathological changes in Huntington's diease
Author(s) -
Furtado Sarah,
Suchowersky Oksana,
Rewcastle N. Barry,
Graham Lisa,
Klimek Mary Lou,
Garber Anthony
Publication year - 1996
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410390120
Subject(s) - putamen , huntington's disease , caudate nucleus , pathology , basal ganglia , pathological , medicine , biology , disease , central nervous system
The discovery of the Huntington's disease (HD) gene has provided the impetus to determine the association between the triplet repeat sequences and clinical manifestations of the disease. The present study is directed toward determining the relationship between the triplet repeat sequences and severity of the neurodegenerative process. Nineteen HD postmortem cases were evaluated for neuropathological changes as well as for the number of trinucleotide repeat sequences, each in a blinded fashion. Each case was assigned a gross grade according to the scale of Vonsattel and colleagues (1985); neuronal counts were then performed on both the caudate and the putamen. For 7 of the postmortem cases, blood had been collected prior to death and was analyzed for the HD gene. For the 12 remaining cases for which blood was unavailable, DNA from the frontal neocortex and striatum was extracted from frozen or formalin‐fixed paraffinized tissue and subsequently analyzed for the HD gene. When correlation was made for age at death, greater numbers of trinucleotide repeats were associated with greater neuronal loss, in both the caudate (r = 0.9641, p < 0.001) and the putamen (r = 0.9652, p < 0.001). When correction was made for disease duration, the correlation was again significant, for both the caudate (r = 0.6396, p < 0.01) and the putamen (r equals; 0.6710, p < 0.001). This suggests that in HD, longer trinucleotide repeat length is associated with a faster rate of deterioration and greater pathological severity. A comparison of trinucleotide repeat length in different brain regions in 4 of the HD postmortem cases associated with greater numbers of repeats consistently demonstrated fewer repeats in the cerebellum than in the frontal cortex, striatum or blood.