Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University (NU) Feinberg School of Medicine, 300 E. Superior St., Tarry 8, Chicago, IL, 60611, USA.
Department of Radiology, NU Feinberg School of Medicine, Chicago, IL, USA.
Acta Neuropathol Commun. 2022 Aug 9;10(1):111. doi: 10.1186/s40478-022-01412-w.
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 F-florbetapir amyloid PET and F-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.
评估体内淀粉样蛋白和 tau PET 成像与死后测量之间的定量关系对于验证具有阿尔茨海默病神经病理改变（ADNC）的临床表型的成像生物标志物的敏感性和特异性至关重要。本研究检查了在具有 ADNC 的原发性进行性失语症（PPA）病例中，体内 F-氟比他滨淀粉样蛋白 PET 和 F-氟托他滨 tau PET 的区域结合与死后淀粉样斑块和神经原纤维缠结（NFT）的立体学计数之间的定量关系，其中神经退行性变不对称地靶向左半球。在死亡前 2 年，一名 63 岁的右利手男性出现语法障碍变体 PPA，接受了氟比他滨和氟托他滨 PET 扫描，以及神经心理学评估和每 6 个月进行一次磁共振成像检查。从 8 个左、右大脑半球脑区定量氟比他滨和氟托他滨 PET 标准摄取值比值（SUVR），并从相应的死后切片中定量淀粉样斑块和 NFT。使用 Pearson 相关性和不对称性测量来检查成像和尸检测量之间的关系。在死亡前的三次就诊中，语言测量值下降，萎缩明显进展。氟比他滨 PET 呈现出非典型的局灶性摄取模式，与 8 个区域的死后淀粉样斑块密度呈显著正相关（r=0.92；p=0.001）。氟托他滨 PET 呈左侧偏侧分布，与 NFT 密度呈显著正相关（r=0.78；p=0.023）。氟托他滨 PET 和 NFT 密度表明 ADNC 具有内侧颞叶保留表现，表明 AD 并不总是靶向内侧颞叶。本研究在 ADNC 的非遗忘表型中增加了额外的证据，表明 AD 正电子发射断层扫描生物标志物氟比他滨和氟托他滨与定量神经病理学之间存在很强的相关性。斑块密度和氟比他滨 PET 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学都表现为弥漫性分布于新皮质。
