Helpern Joseph A, Lee Sang-Pil, Falangola Maria F, Dyakin Victor V, Bogart Adam, Ardekani Babak, Duff Karen, Branch Craig, Wisniewski Thomas, de Leon Mony J, Wolf Oliver, O'Shea Jacqueline, Nixon Ralph A
Nathan S Kline Institute, Orangeburg, New York 10962, USA.
Magn Reson Med. 2004 Apr;51(4):794-8. doi: 10.1002/mrm.20038.
The cerebral deposition of amyloid beta-peptide, a central event in Alzheimer's disease (AD) pathogenesis, begins several years before the onset of clinical symptoms. Noninvasive detection of AD pathology at this initial stage would facilitate intervention and enhance treatment success. In this study, high-field MRI was used to detect changes in regional brain MR relaxation times in three types of mice: 1). transgenic mice (PS/APP) carrying both mutant genes for amyloid precursor protein (APP) and presenilin (PS), which have high levels and clear accumulation of beta-amyloid in several brain regions, starting from 10 weeks of age; 2). transgenic mice (PS) carrying only a mutant gene for presenilin (PS), which show subtly elevated levels of Abeta-peptide without beta-amyloid deposition; and 3). nontransgenic (NTg) littermates as controls. The transverse relaxation time T(2), an intrinsic MR parameter thought to reflect impaired cell physiology, was significantly reduced in the hippocampus, cingulate, and retrosplenial cortex, but not the corpus callosum, of PS-APP mice compared to NTg. No differences in T(1) values or proton density were detected between any groups of mice. These results indicate that T(2) may be a sensitive marker of abnormalities in this transgenic mouse model of AD.
淀粉样β肽在大脑中的沉积是阿尔茨海默病（AD）发病机制的核心事件，在临床症状出现前数年就已开始。在此初始阶段对AD病理进行无创检测将有助于干预并提高治疗成功率。在本研究中，使用高场磁共振成像（MRI）来检测三种类型小鼠脑区磁共振弛豫时间的变化：1）. 携带淀粉样前体蛋白（APP）和早老素（PS）突变基因的转基因小鼠（PS/APP），从10周龄开始，其多个脑区有高水平且明显积累的β淀粉样蛋白；2）. 仅携带早老素（PS）突变基因的转基因小鼠（PS），其β淀粉样肽水平略有升高但无β淀粉样蛋白沉积；3）. 非转基因（NTg）同窝小鼠作为对照。与NTg相比，PS-APP小鼠海马体、扣带回和压后皮质的横向弛豫时间T(2)（一个被认为反映细胞生理功能受损的固有磁共振参数）显著降低，而胼胝体未出现这种情况。在任何小鼠组之间未检测到T(1)值或质子密度的差异。这些结果表明，T(2)可能是这种AD转基因小鼠模型异常的一个敏感标志物。
