阿尔茨海默病脑内β-淀粉样蛋白沉积与血液β-淀粉样蛋白的相关性研究

Correlation study of brainβ-amyloid deposition and bloodβ-amyloid level in Alzheimer′s disease

目的探讨基于体素阿尔茨海默病(AD)PET显像的β-淀粉样蛋白(Aβ)沉积程度与血液生物标志物Aβ间的相关性。方法回顾性分析2015年1月至2018年12月间陆军军医大学大坪医院经临床诊断为AD并行11C-匹兹堡化合物B(11C-PIB)PET显像阳性的患者23例,男9例,女14例,年龄(68.5±9.0)岁,病程(40.9±23.3)个月;轻度患者8例,中重度患者15例。收集患者简易精神状态检查量表(MMSE)评分及临床痴呆评定量表(CDR)评分等临床信息,测量患者血液Aβ42、Aβ40浓度。分析轻度和中重度患者上述指标及Aβ42/Aβ40的差异。对所有患者11C-PIB PET图像进行基于体素的单样本t检验,对轻度和中重度患者11C-PIB PET图像进行基于体素两独立样本t检验,对血液生物标志物指标与11C-PIB PET图像的Aβ沉积程度进行基于体素的Pearson相关分析。结果中重度AD患者MMSE评分低于轻度AD患者[(9.67±4.37)与(17.13±2.80)分;t=4.349,P<0.001],病程长于轻度AD患者[(48.8±23.8)与(26.0±13.5)个月;t=-2.489,P<0.05]。AD患者Aβ主要沉积于双侧额叶、右侧颞叶、右侧枕叶及后扣带回(t值:0.44~0.67,均P<0.001)。相对于血液中Aβ42(r值:-0.33~0,均P>0.05)和Aβ40(r值:-0.41~0,均P>0.05),Aβ42/Aβ40(r值:-0.62~-0.41,0.41~0.66,均P<0.05)与Aβ沉积有更加密切联系。结论基于体素的11C-PIB PET显像分析可以更直接、客观地反映脑内Aβ沉积,AD血液生物标志物Aβ42/Aβ40具有预测脑内Aβ沉积的潜力。

Objective To assess theβ-amyloid(Aβ)deposition of voxel-based PET imaging in Alzheimer′s disease(AD)and its relationships with blood biomarkers(Aβ).Methods From January 2015 to December 2018,a total of 23 AD patients(9 males,14 females,age(68.5±9.0)years;duration:(40.9±23.3)months;8 mild patients,15 moderate or severe patients)who underwent AβPET and with positive imaging results in Daping Hospital,Army Medical University were retrospectively enrolled.The information of Mini-Mental State Examination(MMSE)and Clinical Dementia Rating(CDR)were collected.Blood level of Aβ42,Aβ40 were measured.Differences of those metrics including Aβ42/Aβ40 between mild and moderate or severe patients were compared.For all 11C-Pittsburgh compound B(PIB)PET images,voxel-based one-sample independent t test analyses were performed.Voxel-based two-sample independent t test analyses were also performed between mild and moderate or severe patients.The voxel-based Pearson correlation analyses were run to assess the associations between blood metrics and Aβdeposition of 11C-PIB PET.Results Comparing with mild patients,moderate or severe patients had lower MMSE(9.67±4.37 vs 17.13±2.80;t=4.349,P<0.001)and longer duration((48.8±23.8)vs(26.0±13.5)months;t=-2.489,P<0.05).On voxel-wise analysis,amyloid PET illustrated brain Aβdeposition in bilateral frontal,right temporal,right occipital and posterior cingulate regions(t values:0.44-0.67,all P<0.001).Within AD,Aβ42/Aβ40(r values:from-0.62 to-0.41,0.41-0.66,all P<0.05)were associated with amyloid PET,but not associated with Aβ42(r values:from-0.33 to 0,all P>0.05)or Aβ40(r values:from-0.41 to 0,all P>0.05).Conclusions Based on voxel-wise analysis,11C-PIB PET has comparable value for brain Aβdeposition.Aβ42/Aβ40 has the potential to predict brain Aβdeposition.