Institute of Pathology and Neuropathology, University Hospital Essen, Essen, Germany.
J Alzheimers Dis. 2012;30(4):963-79. doi: 10.3233/JAD-2012-112069.
Alterations in the expression of Reelin (RELN) have been implicated in the pathology of Alzheimer's disease (AD). However, whether these changes are cause or consequence of AD remains to be resolved. To better understand the role of RELN pathway in the development of AD, we examined the expression profile of RELN and its downstream signaling members APOER2, VLDLR, and DAB1 in AD-vulnerable regions of transgenic and wildtype mice as well as in AD patients and controls across disease stages and/or aging. We show that both AD pathology and aging are associated with perturbation of the RELN pathway in a species-, region-, and molecule-specific manner. Further, we show that depletion of RELN, but not its downstream signaling molecules, is detectable long before the onset of amyloid-β pathology in the murine hippocampus and in a pre-clinical AD stage in the human frontal cortex. This early event hints at a possible causative role of RELN decline in the precipitation of AD pathology and supports RELN's potential as a pre-clinical marker for AD.
Reelin (RELN) 的表达变化与阿尔茨海默病 (AD) 的病理学有关。然而，这些变化是 AD 的原因还是结果仍有待解决。为了更好地了解 RELN 通路在 AD 发展中的作用，我们检查了 RELN 及其下游信号分子 APOER2、VLDLR 和 DAB1 在转基因和野生型小鼠的 AD 易损区域以及 AD 患者和对照者在疾病阶段和/或衰老过程中的表达谱。我们发现，AD 病理学和衰老都与 RELN 通路在物种、区域和分子特异性方面的失调有关。此外，我们发现，在小鼠海马体中淀粉样蛋白-β病理学出现之前很久，以及在人类额叶皮层的临床前 AD 阶段，就可以检测到 RELN 的耗竭，但不是其下游信号分子。这一早期事件暗示了 RELN 下降在 AD 病理学形成中的可能因果作用，并支持 RELN 作为 AD 临床前标志物的潜力。
