Spatial patterns of mammalian brain aging: Distribution of cathepsin D-immunoreactive cell bodies and dystrophic dendrites in aging dogs resembles that in Alzheimer's disease
Spatial patterns of mammalian brain aging: Distribution of cathepsin D-immunoreactive cell bodies and dystrophic dendrites in aging dogs resembles that in Alzheimer's disease
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DOI：
10.1002/cne.10795
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发表时间：
2003-09-22
影响因子：
2.5
通讯作者：
Lynch, G
中科院分区：
文献类型：
--
作者：
Bi, XN;Head, E;Lynch, G
在阿尔茨海默病（AD）的早期阶段发现溶酶体酶组织蛋白酶D水平升高，并与神经元内缠结共同发生。目前的研究测试了另一种哺乳动物在衰老过程中是否会出现组织蛋白酶D的增加。比较了0.35 ~ 16岁狗的组织蛋白酶D免疫染色区域脑模式。在中老年犬（大于或等于6岁）的许多前脑部位的神经元细胞体中有明显的免疫阳性物质积累。可以区分为三种类型：(1)密集的聚集体，在细胞体内没有特定的位置；(2)占据细胞体一极的新月形“帽”；(3)从细胞体向顶端树突延伸的非常密集的“尖刺”；这些尖峰只出现在少数区域，最明显的是枕骨下和新皮层第五层。峰值出现在2 ~ 5岁之间，此后随着年龄的增长而稳步增加。在老年人的大脑中发现了棘突，但并不常见；然而，它们在AD大脑中大量存在。这些结果表明，狗的大脑衰老(1)到中年时就已经提前了，(2)不同区域之间的差异显著，(3)至少在某些方面（树突营养不良）在阿尔茨海默病早期已知的病理区域是突出的。结合之前对大鼠的研究结果，这些发现表明，在阿尔茨海默病中观察到的组织蛋白酶D的变化，特别是在颞叶，反映了一种普遍的哺乳动物大脑衰老模式。J. Comp.神经科。(C) 2003 Wiley-Liss, Inc。
Elevated levels of the lysosomal enzyme cathepsin D are found in the early stages of Alzheimer's disease (AD) and co-occur with intraneuronal tangles. The present study tested whether increases in cathepsin D would emerge during aging in another mammalian species. Regional brain patterns of cathepsin D immunostaining were compared in dogs ages 0.35 to 16 years. Accumulations of immunopositive material were evident in neuronal cell bodies in many forebrain sites in middle-age to old dogs (greater than or equal to6 years). Three types could be distinguished: (1) dense aggregates with no particular position within the cell body; (2) crescent-shaped "caps" that occupied one pole of the cell body; and (3) very dense "spikes" that extended from the cell body for variable distances into the apical dendrite; these spikes were found in only a few areas, most notably the subiculum and layer V of neocortex. The spikes appeared between ages 2 and 5 years and increased steadily with age thereafter. Spikes were found in the subiculum in the aged human brain but only infrequently; they were, however, present in large numbers in AD brains. These results established that brain aging in dogs is (1) well advanced by middle age, (2) varies markedly across regions, and (3) in at least some of its aspects (dystrophic dendrites) is prominent in areas known to exhibit pathology early in the course of AD. Combined with previous results for rats, these findings indicated that changes in cathepsin D observed in AD, in particular in the temporal lobe, reflect a generalized mammalian pattern of brain aging. J. Comp. Neurol. (C) 2003 Wiley-Liss, Inc.