Department of Neurology, Michigan State University, East Lansing, MI, USA; Department of Radiology, Michigan State University, East Lansing, MI, USA; Neuroscience Program, Michigan State University, East Lansing, MI, USA.
Neuroscience Program, Michigan State University, East Lansing, MI, USA.
Alzheimers Dement. 2016 Dec;12(12):1250-1258. doi: 10.1016/j.jalz.2016.06.003. Epub 2016 Aug 27.
We evaluated the effect of cerebral amyloid-β (Aβ) deposition in cognitively normal (CN) seniors on regional metabolism of specific brain regions known to be affected by p-tau deposition.
Fluorodeoxyglucose positron emission tomography (FDG-PET), volumetric magnetic resonance imaging scans, and global amyloid standardized uptake value ratios (SUVr) were obtained for 210 CNs from the Alzheimer's Disease Neuroimaging Initiative-2 (ADNI2). Region of interest (ROI) extraction was used to obtain functional SUVr from six bilateral ROIs: amygdala (AM), entorhinal cortex (EC), hippocampus, lateral orbitofrontal, posterior cingulate (PC), and middle temporal gyrus. Every metabolic SUVr set was averaged and analyzed against the corresponding subject's amyloid SUVr. Correlation analyses were conducted on the full group and between APOE ε4-positive and APOE ε4-negative subgroups.
The APOE ε4+ group exhibited significantly higher metabolism in the EC (r = 0.270, P = .038) and AM (r = 0.267, P = .041). When a significance of the difference test was conducted between the APOE ε4+ and APOE ε4-groups, these same regions remained significant: P = .012 and P = .016, respectively. By contrast, the APOE ε4 group displayed only the conventionally expected result of reduced regional metabolism in the PC (r = -0.161, P = .048), with higher Aβ load.
The effect of amyloid positivity on brain metabolism is regionally specific, and APOE ε4 status substantially modulates regional glucose uptake in these regions. The APOE ε4 allele may cause earlier emergence of clinical symptoms in AD via a mechanism that influences regional metabolic demand in specifically those regions where p-tau deposition is known to occur earliest.
我们评估了认知正常（CN）老年人大脑中淀粉样蛋白-β（Aβ）沉积对已知受 p-tau 沉积影响的特定脑区区域代谢的影响。
从阿尔茨海默病神经影像学倡议 2（ADNI2）中获得了 210 名 CN 患者的氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）、容积磁共振成像扫描和全局淀粉样标准化摄取比值（SUVr）。使用感兴趣区域（ROI）提取法从六个双侧 ROI 获得功能 SUVr：杏仁核（AM）、内嗅皮层（EC）、海马体、外侧眶额、后扣带回（PC）和中颞叶。将每个代谢 SUVr 集平均并与相应受试者的淀粉样蛋白 SUVr 进行分析。对全组和 APOE ε4 阳性和 APOE ε4 阴性亚组进行相关性分析。
APOE ε4+组在 EC（r=0.270，P=0.038）和 AM（r=0.267，P=0.041）的代谢显著更高。当在 APOE ε4+和 APOE ε4-组之间进行差异检验的显著性时，这些相同的区域仍然具有显著性：P=0.012 和 P=0.016。相比之下，APOE ε4 组仅显示 PC 区域的区域代谢减少的常规预期结果（r=-0.161，P=0.048），这与较高的 Aβ 负荷有关。
淀粉样蛋白阳性对大脑代谢的影响是区域特异性的，APOE ε4 状态极大地调节了这些区域的葡萄糖摄取。APOE ε4 等位基因可能通过影响 p- tau 沉积最早发生的那些区域的区域代谢需求，从而以一种影响 AD 临床症状早期出现的机制导致 AD 患者的临床症状更早出现。
