Department of Neurology, Center for Clinical Research, University of Ulm, Germany.
Acta Neuropathol. 2011 Feb;121(2):171-81. doi: 10.1007/s00401-010-0789-4. Epub 2010 Dec 15.
Brains of 42 individuals between the ages of 4 and 29 were examined with antibodies (AT8, 4G8) and silver stains for the presence of intraneuronal and extracellular protein aggregates associated with Alzheimer's disease. Thirty-eight of 42 (38/42) cases displayed abnormally phosphorylated tau protein (pretangle material) in nerve cells or in portions of their cellular processes, and 41/42 individuals showed no extracellular amyloid-β protein deposition or neuritic plaques-an individual with Down syndrome was the only exception. In 16/42 cases abnormal tau was found in the transentorhinal region, and in 3/42 cases this site was Gallyas-positive for isolated NFTs (NFT stage I). Of 26 cases that lacked abnormal tau in the transentorhinal region, 4 did not show pretangle material at subcortical sites. The remaining 22 of these same 26 cases, however, had subcortical lesions confined to non-thalamic nuclei with diffuse projections to the cerebral cortex, and, remarkably, in 19/22 individuals the pretangle material was confined to the noradrenergic coeruleus/subcoeruleus complex. Assuming the pretangle alterations are not transient and do not regress, these findings may indicate that the Alzheimer's disease-related pathological process leading to neurofibrillary tangle formation does not begin in the cerebral cortex but, rather, in select subcortical nuclei, and it may start quite early, i.e., before puberty or in early young adulthood.
对 42 名年龄在 4 至 29 岁之间的个体的大脑进行了检查，使用抗体 (AT8、4G8) 和银染法检测与阿尔茨海默病相关的神经元内和细胞外蛋白质聚集体的存在。在 42 例中有 38 例（38/42）显示神经细胞或其细胞过程的部分存在异常磷酸化的 tau 蛋白（预缠结物质），并且 42 例中有 41 例（41/42）个体没有细胞外淀粉样β蛋白沉积或神经原纤维缠结——唐氏综合征个体是唯一的例外。在 16 例中有 16/42 例异常 tau 蛋白在颞叶前区发现，在 3 例中有 3/42 例在这个部位存在孤立的 NFT 的 Gallyas 阳性（NFT 阶段 I）。在 26 例缺乏颞叶前区异常 tau 的病例中，有 4 例在皮质下部位没有预缠结物质。然而，在这 26 例中有 22 例的皮质下病变局限于非丘脑核，具有向大脑皮质弥漫性投射，值得注意的是，在 19/22 例中，预缠结物质局限于去甲肾上腺素能蓝斑/蓝斑下复合体。假设预缠结改变不是短暂的并且不会消退，这些发现可能表明导致神经纤维缠结形成的阿尔茨海默病相关病理过程不是从大脑皮质开始的，而是从特定的皮质下核开始的，而且可能很早就开始了，即青春期前或年轻成年早期。
