Objective: The clinical phenotype of the rare behavioral variant of Alzheimer's disease (bvAD) is insufficiently understood. Given the strong clinico-anatomical correlations of tau pathology in AD, we investigated the distribution of tau deposits in bvAD, in-vivo and ex-vivo, using PET and postmortem examination. Methods: For the tau PET study, seven amyloid-β positive bvAD patients underwent [18F]flortaucipir or [18F]RO948 PET. We converted tau PET uptake values into standardized (W-)scores, by adjusting for age, sex and MMSE in a "typical" memory-predominant AD (n=205) group. W-scores were computed within entorhinal, temporoparietal, medial and lateral prefrontal, insular and whole-brain regions-of-interest, frontal-to-entorhinal and frontal-to-parietal ratios and within intrinsic functional connectivity network templates. For the postmortem study, the percentage of AT8 (tau)-positive area in hippocampus CA1, temporal, parietal, frontal and insular cortices were compared between autopsy-confirmed bvAD (n=8) and typical AD (n=7) patients. Results: Regional W-scores ≥1.96 (corresponding to p<0.05) were observed in three cases, i.e. case #5: medial prefrontal cortex (W=2.13) and anterior default mode network (W=3.79), case #2: lateral prefrontal cortex (W=2.79) and salience network (W=2.77), and case #7: frontal-to-entorhinal ratio (W=2.04). The remaining four cases fell within the normal distributions of the typical AD group. Postmortem AT8 staining indicated no regional differences in phosphorylated tau levels between bvAD and typical AD (all p>0.05). Conclusion: Both in-vivo and ex-vivo, bvAD patients showed heterogeneous patterns of tau pathology. Since key regions involved in behavioral regulation were not consistently disproportionally affected by tau pathology, other factors are more likely driving the clinical phenotype in bvAD.

中文翻译：

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阿尔茨海默氏病行为变异中tau病理学的异质分布

目的：对阿尔茨海默氏病（bvAD）罕见行为变异的临床表型了解不足。鉴于AD的tau病理学与临床解剖学有很强的相关性，我们使用PET和验尸检查了bvAD，体内和离体tau沉积物的分布。方法：在tau PET研究中，对7例淀粉样蛋白β阳性的bvAD患者进行了[18F] flortaucipir或[18F] RO948 PET的治疗。通过调整“典型”以记忆为主的AD（n = 205）组中的年龄，性别和MMSE，我们将tau PET摄取值转换为标准化的（W-）得分。W得分是在内嗅，颞顶，前额内侧和外侧，岛状和全脑感兴趣区域，额叶与肠内和额叶与顶叶的比例以及内在功能连接网络模板中计算的。对于死后研究，比较了尸检确认的bvAD（n = 8）和典型AD（n = 7）患者海马CA1，颞叶，顶叶，额叶和岛叶皮层AT8（tau）阳性面积的百分比。结果：在三种情况下观察到区域W评分≥1.96（对应于p <0.05），即病例＃5：内侧前额叶皮层（W = 2.13）和前默认模式网络（W = 3.79），病例＃2：外侧前额叶皮层（W = 2.79）和显着网络（W = 2.77），案例＃7：额叶与肠内比（W = 2.04）。其余四个案例属于典型AD组的正态分布。死后AT8染色表明bvAD和典型AD之间的磷酸化tau水平没有区域差异（所有p> 0.05）。结论：bvAD患者在体内和体外均显示出tau病理学的异质性模式。