High brain myo-inositol levels in the predementia phase of Alzheimer's disease in adults with Down's syndrome: A 1H MRS study

Wei Huang, Gene E. Alexander, Eileen M. Daly, H. Umesha Shetty, Jack S. Krasuski, Stanley I. Rapoport, Mark B. Schapiro

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


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 languageEnglish (US)
Pages (from-to)1879-1886
Number of pages8
JournalAmerican Journal of Psychiatry
Issue number12
StatePublished - Dec 1999
Externally publishedYes

ASJC Scopus subject areas

  • Psychiatry and Mental health


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