Barrachina M, Maes T, Buesa C, Ferrer I
Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Spain.
Neuropathol Appl Neurobiol. 2006 Oct;32(5):505-16. doi: 10.1111/j.1365-2990.2006.00756.x.
Lysosome-associated membrane protein 1 (LAMP-1) is a glycoprotein highly expressed in lysosomal membranes. The present study was initiated to test LAMP-1 mRNA and protein levels in post mortem frontal cortex (area 8) of Alzheimer's disease (AD) stages I-IIA/B and stages V-VIC of Braak and Braak, compared with age-matched controls. TaqMan PCR assays and Western blots demonstrated upregulation of LAMP-1 mRNA and protein in the cerebral cortex in ADVC. In addition, immunohistochemical studies have shown increased LAMP-1 immunoreactivity in neurones, and in glial cells surrounding senile plaques, in AD cases. Interestingly, LAMP-1 immunoreactivity has little correlation with phosphorylated tau deposition and neurofibrillary tangles (NFTs), as neurones with NFTs were rarely LAMP-1 immunoreactive. In contrast, LAMP-1 expression was enhanced in neurones with granulovacuolar degeneration. Finally, LAMP-1 occurred in microglia and multinucleated giant cells in one AD case in whom amyloid burden was cleared following betaA-peptide immunization. These findings support the participation of lysosomes in betaA-amyloid and, probably, in hyperphosphorylated tau turnover in AD.
溶酶体相关膜蛋白1（LAMP-1）是一种在溶酶体膜上高度表达的糖蛋白。本研究旨在检测阿尔茨海默病（AD）Braak和Braak分期的I-IIA/B期及V-VIC期患者死后额叶皮质（8区）中LAMP-1 mRNA和蛋白水平，并与年龄匹配的对照组进行比较。TaqMan PCR检测和蛋白质印迹法表明，ADVC患者大脑皮质中LAMP-1 mRNA和蛋白上调。此外，免疫组织化学研究显示，AD病例中神经元以及老年斑周围的神经胶质细胞中LAMP-1免疫反应性增加。有趣的是，LAMP-1免疫反应性与磷酸化tau沉积和神经原纤维缠结（NFTs）几乎没有相关性，因为有NFTs的神经元很少有LAMP-1免疫反应性。相反，在有颗粒空泡变性的神经元中LAMP-1表达增强。最后，在1例AD病例中，βA肽免疫后淀粉样蛋白负荷清除，小胶质细胞和多核巨细胞中出现了LAMP-1。这些发现支持溶酶体参与AD中βA淀粉样蛋白以及可能的过度磷酸化tau周转。
