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

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 diseas e. Down's syndrome therefore represents a model for studying preclinical st ages of Alzheimer's disease. Markers that have been investigated in symptom atic Alzheimer's disease are myo-inositol and N-acetyl-aspartate, The autho rs investigated whether abnormal brain levels of myo-inositol and other met abolites occur in the preclinical stages of Alzheimer's disease associated with Down's syndrome. Method: The authors used H-1 magnetic resonance spect roscopy (MRS) with external standards to measure absolute brain metabolite concentrations in 19 nondemented adults with Down's syndrome and 17 age- an d sex-matched healthy comparison subjects. Results: Concentrations of myo-i nositol and choline-containing compounds were significantly higher in the o ccipital and parietal regions of the adults with Down's syndrome than in th e 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-acetylaspartat e levels than the respective younger subjects, although this old-young diff erence was not greater in the Down's syndrome group, Conclusions: The appro ximately 50% higher level of myo-inositol in Down's Syndrome suggests a gen e dose effect of the extra chromosome 21, where the human osmoregulatory so dium/myo-inositol cotransporter gene is located. The even higher myoinosito l level in older adults with Down's syndrome extends to the predementia pha se earlier findings of high myo-inositol levels in symptomatic Alzheimer's disease.