JNNP:阿尔茨海默病行为变异型的tau病理的不均匀分布

2021-04-18 MedSci原创 MedSci原创

患有行为变异型的阿尔茨海默病(bvAD)患者会经历早期显著的行为症状和性格变化,例如去抑制,强迫行为和同理心丧失。由于bvAD的萎缩和低代谢症状主要在颞顶叶区域发生。 有必要更好地了解bvAD表型的神

患有行为变异型的阿尔茨海默病(bvAD)患者会经历早期显著的行为症状和性格变化,例如去抑制,强迫行为和同理心丧失。由于bvAD的萎缩和低代谢症状主要在颞顶叶区域发生。 有必要更好地了解bvAD表型的神经生物学因素。为此,研究牛磺酸沉积在bvAD中的分布至关重要,由于AD的中枢神经病理特征与认知症状的类型和严重程度密切相关 , 在本研究中旨在研究bvAD中tau病理不均匀分布。

在PET研究中,7例淀粉样β阳性的bvAD患者接受了PET检查。我们将tau-PET检查值转换为标准化(W-)分数,并记录AD(n=205)组的年龄、性别和简易精神状态检查结果。在内嗅区、颞顶区、内侧和外侧前额叶区、岛叶区和全脑感兴趣区域、额叶与内嗅区和额叶与顶叶的比值以及内在功能连接网络内计算W评分。在死后研究中,比较尸检证实的bvAD患者(n=8)和典型AD患者(tAD;n=7)海马CA1区、颞叶、顶叶、额叶和岛叶皮质中AT8(tau)阳性区域的百分比。

Figure 1

阿尔茨海默病行为变异型(bvAD,单独显示)与 阿尔茨海默病被试者(tAD,显示为该组的平均值)大脑中tau病理学的分布。

Figure 4

bvAD和 AD患者死后tau免疫组化研究

在tau-PET研究中,bvAD患者中有6/7(85.7%)为男性,tAD患者中有48.3%为男性。bvAD组年龄在59~80岁(平均69.1±8.4岁),tAD组平均67.8±7.7岁。 7例bvAD中3/7例APOEε4阳性,1例bvAD中3/7例APOEε3纯合子缺失,70%的tAD中APOEε4阳性。bvAD患者出现bvFTD症状的范围为2到6个,其中最常见的症状是冷漠(n=6),其次是去抑制(n=5)、移情能力丧失、强迫和多嘴(所有n=3)和执行障碍(n=1)。bvAD病例1的NPI评分为20分,病例2的NPI评分为41分,而tAD的NPI评分中位数为7分(n=29)。bvAD病例#6的MBI-C评分缺失,病例#7的MBI-C评分为18,bvAD组的平均死亡年龄为66.6±6.0,tAD组的平均死亡年龄为69.1±3.3。bvAD组病程(6.3±3.6年)略长于tAD组(4.6±3.3年)。病例5:内侧前额叶皮质(W=2.13),例2:外侧前额叶皮质(W=2.79),例7:额叶-内嗅值(W=2.04)。其余4例属于tAD组的正态分布。死后AT8染色显示bvAD和tAD之间磷酸化tau水平没有组水平的区域差异(p>0.05)。

无论是体内还是体外,bvAD患者的tau病理分布均不均匀。由于参与行为调节的关键区域并不总是受到tau病理学的不成比例的影响,其他因素更有可能导致bvAD的临床表型。

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    2021-12-04 zhmscau
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    2021-04-20 hb2008ye

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