近些年，低密度脂蛋白受体（LDLR）获得了很高的关注，主要是因为它与冠状动脉心脏疾病和动脉粥样硬化有关。根据发布在12月10日Neuron上的一篇文章，LDLR似乎也与退化性大脑疾病有关。这项新的研究表明，LDLR能减少与老年痴呆（AD）相关的大脑变化，该研究为这类无法治愈的疾病提供了新的治疗策略。
淀粉样β蛋白（Aβ）是引起AD的主要原因，Aβ堆积会造成神经元的破坏，因此它被认为是疾病发病机理的首要因素。此外，载脂蛋白E(apoE)，是一个已经确定的晚发型AD的遗传风险因子，其参与脂肪的代谢和运输。先前的研究已经涉及Aβ堆积中的apoE。
调节控制apoE代谢的蛋白功能将可能改变淀粉样堆积的范围，并最终影响疾病的发展。这项研究的负责人是来自华盛顿大学医学院的David M. Holtzman博士，据他介绍，低密度的脂蛋白受体能够绑定到apoE上，但是其对AD发病机制的潜在影响还不是很清楚。
Holtzman博士和他的同事基因改造了一种大脑中LDLR过表达的老鼠，使其表现出与AD相关的病理学变化。结果发现，LDLR过表达导致了Aβ聚集的减少，淀粉状蛋白斑的形成，并出现神经炎症反应。
该研究结果清晰地表明了大脑中LDLR过表达的有利影响，或有助于在未来开发出新的退化型神经疾病治疗药物，对外周组织中的LDLR进行调控。（生物谷Bioon.com）
生物谷推荐原始出处：
Neuron, Volume 63, doi:10.1016/j.neuron.2009.06.026
The Role of Apolipoprotein E in Alzheimer's Disease
Jungsu Kim1, Jacob M. Basak1 and David M. Holtzman1, ,
1 Department of Neurology, Developmental Biology, Hope Center for Neurological Disorders, Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA
The ε4 allele of apolipoprotein E (APOE) is the major genetic risk factor for Alzheimer's disease (AD). Although there have been numerous studies attempting to elucidate the underlying mechanism for this increased risk, how apoE4 influences AD onset and progression has yet to be proven. However, prevailing evidence suggests that the differential effects of apoE isoforms on Aβ aggregation and clearance play the major role in AD pathogenesis. Other potential mechanisms, such as the differential modulation of neurotoxicity and tau phosphorylation by apoE isoforms as well as its role in synaptic plasticity and neuroinflammation, have not been ruled out. Inconsistent results among studies have made it difficult to define whether the APOE ε4 allele represents a gain of toxic function, a loss of neuroprotective function, or both. Therapeutic strategies based on apoE propose to reduce the toxic effects of apoE4 or to restore the physiological, protective functions of apoE.
