From the Avid Radiopharmaceuticals (CMC, ML, APC, ADJ, MAM, MJP, DMS), Philadelphia, Pennsylvania; Banner Sun Health Research Institute (BND, GS, MM, MNS, LIS, TGB), Sun City, Arizona; Biospective Inc. and Montreal Neurological Institute (BJB, SPZ), McGill University, Montreal, Canada; Duke University Medical Center (REC, PMD), Durham, North Carolina; Banner Alzheimer's Institute (ASF, EMR), Phoenix, Arizona; Nova SE University (CHS), Ft Lauderdale, Florida; and Rush University Medical Center (JAS), Chicago, Illinois.
J Neuropathol Exp Neurol. 2014 Jan;73(1):72-80. doi: 10.1097/NEN.0000000000000028.
Neuropathologic heterogeneity is often present among Alzheimer disease (AD) patients. We sought to determine whether amyloid imaging measures of AD are affected by concurrent pathologies. Thirty-eight clinically and pathologically defined AD and 17 nondemented patients with quantitative florbetapir F-18 (F-AV-45) positron emission tomography (PET) imaging during life and postmortem histological β-amyloid quantification and neuropathologic examination were assessed. AD patients were divided on the basis of concurrent pathologies, including those with Lewy bodies (LBs) (n = 21), white matter rarefaction (n = 27), severe cerebral amyloid angiopathy (n = 11), argyrophilic grains (n = 5), and TAR DNA binding protein-43 inclusions (n = 18). Many patients exhibited more than 1 type of concurrent pathology. The ratio of cortical to cerebellar amyloid imaging signal (SUVr) and immunohistochemical β-amyloid load were analyzed in 6 cortical regions of interest. All AD subgroups had strong and significant correlations between SUVr and histological β-amyloid measures (p μ 0.001). All AD subgroups had significantly greater amyloid measures versus nondemented patients, and mean amyloid measures did not significantly differ between AD subgroups. When comparing AD cases with and without each pathology, AD cases with LBs had significantly lower SUVr measures versus AD cases without LBs (p = 0.002); there were no other paired comparison differences. These findings indicate that florbetapir-PET imaging is not confounded by neuropathological heterogeneity within AD.
神经病理学异质性在阿尔茨海默病(AD)患者中经常存在。我们试图确定 AD 的淀粉样蛋白成像测量是否受并发病理的影响。38 名临床和病理定义明确的 AD 患者和 17 名非痴呆患者在生前进行了定量氟比他滨 F-18(F-AV-45)正电子发射断层扫描(PET)成像,并在死后进行了β-淀粉样蛋白定量和神经病理学检查。AD 患者根据并发病理进行了分组,包括伴有路易体(LB)的患者(n=21)、白质稀疏的患者(n=27)、严重脑淀粉样血管病的患者(n=11)、颗粒状银染(n=5)和 TAR DNA 结合蛋白-43 包涵体的患者(n=18)。许多患者表现出多种类型的并发病理。分析了 6 个皮质感兴趣区的皮质与小脑淀粉样蛋白成像信号(SUVr)和免疫组织化学β-淀粉样蛋白负荷。所有 AD 亚组的 SUVr 与组织学β-淀粉样蛋白测量之间均存在强且显著的相关性(pμ0.001)。所有 AD 亚组的淀粉样蛋白测量值均显著高于非痴呆患者,且 AD 亚组之间的平均淀粉样蛋白测量值无显著差异。当比较有和无每种病理的 AD 病例时,有 LB 的 AD 病例的 SUVr 测量值显著低于无 LB 的 AD 病例(p=0.002);没有其他配对比较差异。这些发现表明,氟比他滨-PET 成像不受 AD 内神经病理学异质性的影响。