Objective: An extra portion of chromosome 21 in Down's syndrome leads to a dementia in later life that is phenotypically similar to Alzheimer's disease. Down's syndrome therefore represents a model for studying preclinical stages of Alzheimer's disease. Markers that have been investigated in symptomatic Alzheimer's disease are myo-inositol and N- acetylaspartate. The authors investigated whether abnormal brain levels of myo-inositol and other metabolites occur in the preclinical stages of Alzheimer's disease associated with Down's syndrome. Method: The authors used 1H magnetic resonance spectroscopy (MRS) with external standards to measure absolute brain metabolite concentrations in 19 nondemented adults with Down's syndrome and 17 age- and sex-matched healthy comparison subjects. Results: Concentrations of myo-inositol and choline-containing compounds were significantly higher in the occipital and parietal regions of the adults with Down's syndrome than in the comparison subjects. Within the Down's syndrome group, older subjects (42-62 years, N=11) had higher myo-inositol levels than younger subjects (28-39 years, N=8). Older subjects in both groups had lower N-acetylaspartate levels than the respective younger subjects, although this old-young difference was not greater in the Down's syndrome group. Conclusions: The approximately 50% higher level of myo-inositol in Down's syndrome suggests a gene dose effect of the extra chromosome 21, where the human osmoregulatory sodium/myo-inositol cotransporter gene is located. The even higher myoinositol level in older adults with Down's syndrome extends to the predementia phase earlier findings of high myo-inositol levels in symptomatic Alzheimer's disease.
|Original language||English (US)|
|Number of pages||8|
|Journal||American Journal of Psychiatry|
|State||Published - Dec 1 1999|
ASJC Scopus subject areas
- Psychiatry and Mental health