Abstract：
Quantification of in vivo amyloid and tau PET imaging relationships with postmortem measurements are critical for validating the sensitivity and specificity imaging biomarkers across clinical phenotypes with Alzheimer disease neuropathologic change (ADNC). This study examined the quantitative relationship between regional binding of in vivo 18F-florbetapir amyloid PET and 18F-flortaucipir tau PET with postmortem stereological counts of amyloid plaques and neurofibrillary tangles (NFT) in a case of primary progressive aphasia (PPA) with ADNC, where neurodegeneration asymmetrically targets the left hemisphere. Beginning 2 years prior to death, a 63-year-old right-handed man presenting with agrammatic variant PPA underwent a florbetapir and flortaucpir PET scan, and neuropsychological assessments and magnetic resonance imaging sessions every 6 months. Florbetapir and flortaucpir PET standard uptake value ratios (SUVRs) were quantified from 8 left and right hemisphere brain regions with stereological quantification of amyloid plaques and NFTs from corresponding postmortem sections. Pearson\'s correlations and measures of asymmetry were used to examine relationships between imaging and autopsy measurements. The three visits prior to death revealed decline of language measures, with marked progression of atrophy. Florbetapir PET presented with an atypical focal pattern of uptake and showed a significant positive correlation with postmortem amyloid plaque density across the 8 regions (r = 0.92; p = 0.001). Flortaucipir PET had a left-lateralized distribution and showed a significant positive correlation with NFT density (r = 0.78; p = 0.023). Flortaucipir PET and NFT density indicated a medial temporal lobe sparing presentation of ADNC, demonstrating that AD does not always target the medial temporal lobe. This study adds additional evidence, in a non-amnestic phenotype of ADNC, that there is a strong correlation between AD PET biomarkers, florbetapir and flortaucipir, with quantitative neuropathology. The atypical and focal presentation of plaque density and florbetapir PET uptake suggests not all amyloid pathology presents as diffuse across neocortex.
摘要：
体内淀粉样蛋白和tauPET成像与事后测量的关系的定量对于验证具有阿尔茨海默病神经病理变化（ADNC）的临床表型的敏感性和特异性成像生物标志物至关重要。这项研究研究了在原发性进行性失语（PPA）的情况下，体内18F-florbetapir淀粉样蛋白PET和18F-flortaucipirtauPET的区域结合与宰后立体计数的淀粉样斑块和神经原纤维缠结（NFT）之间的定量关系。神经变性不对称地瞄准左半球。从死亡前两年开始，一名63岁的右撇子男子出现了农艺变异的PPA，接受了florbetapir和flortaucpirPET扫描，每6个月进行一次神经心理学评估和磁共振成像。Florbetapir和flortaucpirPET标准摄取值比率（SUVR）从8个左右半球大脑区域进行定量，并从相应的死后切片对淀粉样蛋白斑块和NFT进行立体定量。Pearson的相关性和不对称性测量用于检查成像和尸检测量之间的关系。死亡前的三次探视显示语言指标下降，有明显的萎缩进展。FlorbetapirPET表现出非典型的局部摄取模式，并与8个区域的死后淀粉样斑块密度显着正相关（r=0.92；p=0.001）。FlortaucipirPET具有左侧分布，并且与NFT密度呈显着正相关（r=0.78；p=0.023）。FlortaucipirPET和NFT密度显示颞叶内侧保留ADNC，证明AD并不总是针对内侧颞叶。这项研究增加了额外的证据，在ADNC的非遗忘表型中，ADPET生物标志物之间有很强的相关性，florbetapir和flortaucipir,定量神经病理学。斑块密度和florbetapirPET摄取的非典型和局灶性表现表明，并非所有淀粉样蛋白病理都表现为在新皮质中弥漫性。
