Katsuno T, Morishima-Kawashima M, Saito Y, Yamanouchi H, Ishiura S, Murayama S, Ihara Y
Department of Neuropathology, Faculty of Medicine, Graduate School of Arts and Science, University of Tokyo, Tokyo, Japan.
Neurology. 2005 Feb 22;64(4):687-92. doi: 10.1212/01.WNL.0000151958.79884.86.
Previous studies have repeatedly described that neurofibrillary tangles arise earlier than senile plaques (SPs) in the entorhinal cortex, but one study suggested that SPs, if present, enhance the former lesions. All of these studies were performed at the histologic or immunocytochemical level, which may not accurately reflect the actual levels of amyloid beta-protein (Abeta) and tau.
To determine whether there is significant interaction between Abeta and tau in the human entorhinal cortex with regard to the Braak stage.
Biochemical studies were conducted on 50 brains from elderly people, who were mainly at Braak stages I to III. All the cases were examined neuropathologically and staged according to Braak and Braak. A small piece of brain tissue for each case was dissected from the anterior portion of the right entorhinal cortex. The amounts of tau and Abeta in the insoluble fraction of the tissue were quantified using western blotting.
The levels of tau and possibly Abeta42 in the entorhinal cortex appeared to rise steeply at approximately age 75. The levels of insoluble tau increased as the Braak stage increased from I to II; however, it had a tendency to remain between stages II and III. The levels of Abeta42 showed a small increase, whereas those of Abeta40 increased continuously as the Braak stage advanced. In contrast, the extent of Abeta42 accumulation increased with increasing Braak stage for SPs. There was no significant correlation between the levels of insoluble tau and Abeta42 in the entorhinal cortex. Even if Abeta did not accumulate to significant extents, substantial accumulation of insoluble tau occurred.
Accumulations of tau and amyloid beta-protein occur independently in the human entorhinal cortex.
既往研究反复描述内嗅皮质中神经原纤维缠结比老年斑出现更早，但有一项研究表明，如果存在老年斑，会加重前者病变。所有这些研究均在组织学或免疫细胞化学水平进行，可能无法准确反映β淀粉样蛋白（Aβ）和tau的实际水平。
确定在人类内嗅皮质中，Aβ和tau在Braak分期方面是否存在显著相互作用。
对50例主要处于Braak I至III期的老年人脑进行生化研究。所有病例均经神经病理学检查并根据Braak和Braak分期。从右侧内嗅皮质前部切取每例一小块脑组织。采用蛋白质印迹法对组织不溶性部分中的tau和Aβ含量进行定量。
内嗅皮质中tau以及可能的Aβ42水平在约75岁时似乎急剧上升。不溶性tau水平随Braak分期从I期增加到II期而升高；然而，在II期和III期之间有保持稳定的趋势。Aβ42水平有小幅升高，而Aβ40水平随Braak分期进展持续升高。相比之下，对于老年斑，Aβ42的积累程度随Braak分期增加而增加。内嗅皮质中不溶性tau水平与Aβ42水平之间无显著相关性。即使Aβ没有大量积累，不溶性tau也会大量积累。
tau和β淀粉样蛋白在人类内嗅皮质中独立积累。
