Stages of the Pathologic Process in Alzheimer Disease: Age Categories From 1 to 100 Years
Stages of the Pathologic Process in Alzheimer Disease: Age Categories From 1 to 100 Years
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DOI：
10.1097/nen.0b013e318232a379
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发表时间：
2011-11-01
影响因子：
3.2
通讯作者：
Del Tredici, Kelly
中科院分区：
文献类型：
--
作者：
Braak, Heiko;Thal, Dietmar R.;Del Tredici, Kelly
用免疫细胞化学和Galyas银染法检测2,332例年龄在1~100岁之间的未入选脑组织中的tau异常，用免疫细胞化学和Campbell-Switzer染色检测β-淀粉样蛋白。共有342例Galyas染色为阴性，但当再次检测AT8时，只有10例免疫阴性。58例皮质下tau主要位于蓝斑，但未见皮质tau异常(a-c期)。皮质受累(神经突起中的tau异常)最先发现于经鼻嗅区(1a期，38例)。经鼻内锥体细胞呈角质状(1b期，236例)。Pretanges逐渐发展为嗜银神经原纤维缠结(NFTs)，与NFT分期I至VI期平行。局限于皮质下部位的Pretangles主要见于较年轻的年龄。在全部病例中，1,031例(44.2%)有β-淀粉样斑块。第一个斑块出现在脑干紧张症发作后的大脑皮层。在所有病例中，4%的斑块通常在40多岁时发展，在第十个十年达到顶峰(75%)。β-淀粉样斑块和NFT显著相关(p<；0.0001)。这些数据表明，与散发性阿尔茨海默病相关的焦虑症可能比之前认为的更早开始，可能发生在较低的脑干，而不是经鼻鼻区域。
Two thousand three hundred and thirty two nonselected brains from 1- to 100-year-old individuals were examined using immunocytochemistry (AT8) and Gallyas silver staining for abnormal tau; immunocytochemistry (4G8) and Campbell-Switzer staining were used for the detection of beta-amyloid. A total of 342 cases was negative in the Gallyas stain but when restaged for AT8 only 10 were immunonegative. Fifty-eight cases had subcortical tau predominantly in the locus coeruleus, but there was no abnormal cortical tau (subcortical Stages a-c). Cortical involvement (abnormal tau in neurites) was identified first in the transentorhinal region (Stage 1a, 38 cases). Transentorhinal pyramidal cells displayed pretangle material (Stage 1b, 236 cases). Pretangles gradually became argyrophilic neurofibrillary tangles (NFTs) that progressed in parallel with NFT Stages I to VI. Pretangles restricted to subcortical sites were seen chiefly at younger ages. Of the total cases, 1,031 (44.2%) had beta-amyloid plaques. The first plaques occurred in the neocortex after the onset of tauopathy in the brainstem. Plaques generally developed in the 40s in 4% of all cases, culminating in their tenth decade (75%). beta-amyloid plaques and NFTs were significantly correlated (p < 0.0001). These data suggest that tauopathy associated with sporadic Alzheimer disease may begin earlier than previously thought and possibly in the lower brainstem rather than in the transentorhinal region.