Department of Psychological Medicine, Section of Brain Maturation, Institute of Psychiatry, King's College London, London, England, UK; Department of Psychology, Institute of Psychiatry, King's College London, UK; NIHR Biomedical Research Center for Mental Health at the South London and Maudsley NHS Foundation Trust and King's College London, Institute of Psychiatry, London, UK.
MRC Centre for Neurodegeneration Research, Section of Old Age Psychiatry, Institute of Psychiatry, King's College London, UK.
Neuroimage. 2011 Jul 1;57(1):63-68. doi: 10.1016/j.neuroimage.2011.03.073. Epub 2011 Apr 12.
It is poorly understood why people with Down syndrome (DS) are at extremely high-risk of developing Alzheimer's disease (AD) compared to the general population. One explanation may be related to their extra copy of risk factors modulated by chromosome 21. Myo-inositol (mI), whose transporter gene is located on chromosome 21, has been associated with dementia in the non-DS population; however, nobody has contrasted brain mI in DS with (DS+) and without (DS-) dementia to other non-DS groups. Our primary aim was to compare the hippocampal concentration of mI ([mI]) and other brain metabolites such as N-acetylaspartate (NAA; a proxy measure of neuronal density and mitochondrial function) in DS+, DS-, and age-matched healthy controls using proton Magnetic Resonance Spectroscopy (((1))H-MRS). We compared hippocampal [mI] and other metabolites in 35 individuals with genetically-confirmed DS [DS+ (n=17, age=53±6) and DS- (n=18, age=47±8)] to age-matched healthy controls (n=13, age=51±10) adjusting for proportion of the MRS voxel occupied by cerebrospinal spinal fluid, and gray/white matter. DS+ had a significantly higher [mI] than both DS- and healthy controls. In contrast neither DS+ nor DS- differed significantly from controls in [NAA] (although NAA in DS+ was significantly lower than DS-). Our secondary aim of comparing brain metabolites in DS+ and DS- to Alzheimer's disease (AD; n=39; age=77±5) revealed that the DS+ group had significantly elevated [mI] compared to AD or DS-. [mI] may modify risk for dementia in this vulnerable population.
唐氏综合征（DS）患者罹患阿尔茨海默病（AD）的风险极高，但其发病机制尚不清楚。一种解释可能与 21 号染色体上调节风险因素的额外拷贝有关。肌醇（mI），其转运体基因位于 21 号染色体上，与非 DS 人群的痴呆有关；然而，目前还没有人将 DS 患者（DS+）和非痴呆 DS 患者（DS-）的脑 mI 与其他非 DS 组进行对比。我们的主要目的是使用质子磁共振波谱（1H-MRS）比较 DS+、DS-和年龄匹配的健康对照组的海马 mI([mI])和其他脑代谢物（如 N-乙酰天冬氨酸[NAA]；神经元密度和线粒体功能的替代指标）的浓度。我们比较了 35 名经基因证实的 DS 患者[DS+（n=17，年龄 53±6）和 DS-（n=18，年龄 47±8）]和年龄匹配的健康对照组（n=13，年龄 51±10）的海马 [mI]和其他代谢物，调整了 MRS 体素中脑脊液的比例和灰质/白质。DS+的 [mI]显著高于 DS-和健康对照组。相反，DS+和 DS-与对照组在 [NAA]方面没有显著差异（尽管 DS+的 NAA 显著低于 DS-）。我们将 DS+和 DS-的脑代谢物与 AD（n=39，年龄 77±5）进行比较的次要目的是发现 DS+组的 [mI]显著高于 AD 或 DS-。[mI]可能会改变该脆弱人群发生痴呆的风险。
