Elobeid Adila, Laurell Katarina, Cesarini Kristina Giuliana, Alafuzoff Irina
From the Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå (KL); Department of Immunology, Genetics, and Pathology (AE, IA) and Division of Neurosurgery, Department of Neuroscience, Uppsala University (KGC); and Department of Pathology, Uppsala University Hospital (AE, IA), Uppsala, Sweden.
J Neuropathol Exp Neurol. 2015 May;74(5):470-9. doi: 10.1097/NEN.0000000000000191.
Alzheimer disease (AD)-related pathology was assessed in cortical biopsy samples of 111 patients with idiopathic normal-pressure hydrocephalus. Alzheimer disease hallmark lesions-β-amyloid (Aβ) and hyperphosphorylated tau (HPtau)-were observed in 47% of subjects, a percentage consistent with that for whole-brain assessment reported postmortem in unselected cohorts. Higher-immunostained area fraction of AD pathology corresponded with lower preoperative mini-mental state examination scores. Concomitant Aβ and HPtau pathology, reminiscent of that observed in patients with AD, was observed in 22% of study subjects. There was a significant correlation between Aβ-immunostained area fraction in tissue and Aβ42 (42-amino-acid form of Aβ) in cerebrospinal fluid (CSF). Levels of Aβ42 were significantly lower in CSF in subjects with concomitant Aβ and HPtau pathology compared with subjects lacking pathology. Moreover, a significant correlation between HPtau-immunostained area fraction and HPtau in CSF was noted. Both HPtau and total tau were significantly higher in CSF in subjects with concomitant Aβ and HPtau pathology compared with subjects lacking pathology. The 42-amino-acid form of Aβ (Aβ42) and HPtau in CSF were the most significant predictors of the presence of AD pathology in cortical biopsies. Long-term follow-up studies are warranted to assess whether all patients with idiopathic normal-pressure hydrocephalus with AD pathology progress to AD and to determine the pathologic substrate of idiopathic normal-pressure hydrocephalus.
对111例特发性正常压力脑积水患者的皮质活检样本进行了阿尔茨海默病（AD）相关病理学评估。在47%的受试者中观察到了阿尔茨海默病标志性病变——β-淀粉样蛋白（Aβ）和过度磷酸化tau蛋白（HPtau），这一比例与未选择队列中死后全脑评估报告的比例一致。AD病理学免疫染色面积分数越高，术前简易精神状态检查评分越低。在22%的研究对象中观察到了同时存在的Aβ和HPtau病理学，这让人联想到在AD患者中观察到的情况。组织中Aβ免疫染色面积分数与脑脊液（CSF）中的Aβ42（42个氨基酸形式的Aβ）之间存在显著相关性。与无病理学表现的受试者相比，同时存在Aβ和HPtau病理学表现的受试者脑脊液中Aβ42水平显著降低。此外，还注意到HPtau免疫染色面积分数与脑脊液中HPtau之间存在显著相关性。与无病理学表现的受试者相比，同时存在Aβ和HPtau病理学表现的受试者脑脊液中的HPtau和总tau均显著升高。脑脊液中的Aβ42（42个氨基酸形式的Aβ）和HPtau是皮质活检中AD病理学存在的最显著预测指标。有必要进行长期随访研究，以评估所有患有AD病理学的特发性正常压力脑积水患者是否会进展为AD，并确定特发性正常压力脑积水的病理基础。
