Arai Y, Suzuki A, Mizuguchi M, Takashima S
Department of Mental Retardation and Birth Defect Research, National Center for Neurology and Psychiatry, Tokyo, Japan.
Brain Dev. 1997 Jun;19(4):290-4. doi: 10.1016/s0387-7604(97)00559-7.
We studied immunohistochemically the expression of beta-amyloid precursor protein (APP) in the frontal lobes of 18 Down syndrome (DS) patients (20 gestation weeks (GW) to 50 years) and 15 controls (17 GW to 50 years) using six purified antibodies against the secretory forms (N-terminal, N-Amy and Amy540), the Kunitz-type protease inhibitor (KPI) domain, residues 1-28 of beta protein (Affi28), and the carboxyl-terminal fragment (Ac) of APP. In the cortex of fetuses, neonates and infants, immunoreactivity for N-Amy and Ac was observed in both neurons and glial cells, and that for Affi28 in glial cells in the subpial layer in both DS patients and controls suggesting the functioning role of APP was a growth factor. This immunoreactivity disappeared in childhood and reappeared in adulthood in only DS patients. The earlier reappearance of those in DS patients from a young adult age than in normal controls may result from a gene dosage effect, since APP is encoded on chromosome 21. The N-Amy, Amy540, Affi28 and Ac immunoreactivity in glial cells in the developing white matter in the both DS patients and controls may be associated with myelination glia. Immunoreactivity for KPI was noted on the tunica media of the arteries from the neonatal period to adulthood in only DS patients. In senile plaques in DS patients, N-terminal and Affi28 immunoreactivity became detectable at the age of 32 years. N-terminal immunoreactivity in the senile plaques was noted along the periphery of the senile plaques, while that for Affi28 was around the amyloid core. Thus, each fragment of APP exhibited a different localization and time course of immunohistochemical expression. The results indicated that APP plays a role in neuronal development and that its earlier reappearance in adult DS patients is associated with the regeneration process related to aging.
我们使用六种针对分泌形式（N 端、N-Amy 和 Amy540）、Kunitz 型蛋白酶抑制剂（KPI）结构域、β蛋白 1-28 位残基（Affi28）以及 APP 羧基末端片段（Ac）的纯化抗体，对 18 名唐氏综合征（DS）患者（妊娠 20 周（GW）至 50 岁）和 15 名对照者（17GW 至 50 岁）额叶中β-淀粉样前体蛋白（APP）的表达进行了免疫组织化学研究。在胎儿、新生儿和婴儿的皮质中，DS 患者和对照者的神经元和胶质细胞中均观察到 N-Amy 和 Ac 的免疫反应性，在软膜下层的胶质细胞中观察到 Affi28 的免疫反应性，提示 APP 的功能作用是一种生长因子。这种免疫反应性在儿童期消失，并仅在成年 DS 患者中再次出现。DS 患者从青年期比正常对照者更早出现这些情况可能是由于基因剂量效应，因为 APP 由 21 号染色体编码。DS 患者和对照者发育中的白质中胶质细胞的 N-Amy、Amy540、Affi28 和 Ac 免疫反应性可能与髓鞘形成胶质细胞有关。仅在 DS 患者中，从新生儿期到成年期的动脉中膜均观察到 KPI 的免疫反应性。在 DS 患者的老年斑中，32 岁时可检测到 N 端和 Affi28 的免疫反应性。老年斑中的 N 端免疫反应性沿老年斑周边观察到，而 Affi28 的免疫反应性在淀粉样核心周围观察到。因此，APP 的每个片段都表现出不同的免疫组织化学表达定位和时间进程。结果表明，APP 在神经元发育中起作用，其在成年 DS 患者中的早期再次出现与衰老相关的再生过程有关。
