More than 7 million people are expected to be living with Alzheimer’s disease (AD) by 2025 in the USA alone, presenting significant social and economic challenges. The age-related neurological disorder is characterized by memory loss and dementia yet, despite its prevalence, the underlying causes of AD are largely unknown and no preventative treatments currently exist.
患有AD的人的大脑以淀粉样蛋白β（Aβ）聚集体（也称为斑块）的存在为标志，这些淀粉样蛋白β（Aβ）骨料（也称为斑块）破坏了突触功能，最终被认为会引发一系列导致神经变性和痴呆的事件。人类和动物模型中的证据表明，载脂蛋白E（APOE）基因的ε4等位基因增强了淀粉样蛋白病理学并增加了斑块在大脑中的积累。实际上，除了增加AD患病率外，APOE4的存在也被认为降低了疾病发作的时代。然而，在哪个阶段APOE4对淀粉样蛋白病理的影响最强。
Professor Bu and his colleague’s latest research suggests that the expression of APOE4 plays a critical role in driving amyloid pathology during the earliest stages of the disease. We asked him a few questions about this research:
Which models did you develop to study the varying effects of APOE4?
“We used a set of newly developed mouse models that allow us to turn on or off of apoE isoform expression at different stages of the amyloid pathology.”
你的,随着最重要的发现是什么ch?
“That apoE4 drives amyloid pathology at the initial seeding stage rather than by promoting the growth of amyloid.”
What are the major implications of this work?
“Our findings suggest that targeting apoE4 to reduce amyloid pathology needs to focus on early prevention.”
What future work do you have planned to continue this research?
“We plan to address the molecular mechanism underlying apoE4 effects on amyloid during seeding and develop strategies for intervention and drug development.”
Professor Bu’s research was presented at Neuroscience 2016, the annual meeting of the Society for Neuroscience and the world’s largest source of emerging news about brain science and health.
For the lay public reading this, what time frame qualifies as the early seeding stage?
The experiments were performed in animals. In the specific mouse model we used, the seeding stage is around 3-6 months. In humans, amyloid can appear years even decades before the dementia symptoms and is influenced by APOE genotype. APOE4 carriers start developing amyloid in their 40s-50s, whereas those without the APOE4 gene typically develop amyloid after 60 years of age. The age when amyloid starts developing is close to the so called “seeding stage”.