南佛罗里达大学精神病学和行为神经科学系研究小组发现淀粉样前体蛋白（APP）片段——SAPP-α与阿尔茨海默氏症有关。SAPP-α似乎能调控自己的生产。这一发现对通过调控APP预防或治疗阿尔茨海默氏症具有重要意义。
相关研究结果发表于今天的Nature Communications杂志上。
全世界估计有30万人阿尔茨海默氏症，而在美国这一人数为5万。随着“婴儿潮”一代的老龄化，在美国因年龄增长导致的疾病的患病率预计在未来几年大幅增加。目前，有没有积极的疾病预防、治疗手段能扭转或阻止阿尔茨海默氏病。
论文主要作者、USF卫生署的精神病学和行为神经科学Demian Obregon博士说：阿尔茨海默氏症相关的危险因素导致SAPP-α水平下降，从而导致Aβ的形成过程中一种关键酶过度活跃。
在细胞实验初步研究以及后续使用阿尔茨海默氏病的基因工程小鼠的研究中，研究人员发现，中和SAPP-α能增强Aβ的形成。SAPP-α的这种活性功能依赖于SAPP-α与APP转换酶（BACE1）之间发生作用的功能。当这种SAPP-α与APP转换酶之间的互动被打破时，Aβ的形成会恢复到正常水平。
作者认为通过监测和纠正SAPP-α的低水平或通过加强SAPP-α与BACE的相互作用，将来老年痴呆症或可预防和治疗。（生物谷：Bioon）
doi:10.1038/ncomms1781
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Soluble amyloid precursor protein-α modulates β-secretase activity and amyloid-β generation
Demian Obregon,Huayan Hou,Juan Deng,Brian Giunta,Jun Tian,Donna Darlington,Md Shahaduzzaman,Yuyuan Zhu,Takashi Mori,Mark P. Mattson& Jun Tan
In sporadic age-related forms of Alzheimer's disease (AD), it is unclear why amyloid-β (Aβ) peptides accumulate. Here we show that soluble amyloid precursor protein-α (sAPP-α) decreases Aβ generation by directly associating with β-site APP-converting enzyme (BACE)1, thereby modulating APP processing. Whereas specifically targeting sAPP-α using antibodies enhances Aβ production; in transgenic mice with AD-like pathology, sAPP-α overexpression decreases β-amyloid plaques and soluble Aβ. In support, immunoneutralization of sAPP-α increases APP amyloidogenic processing in these mice. Given our current findings, and because a number of risk factors for sporadic AD serve to lower levels of sAPP-α in brains of AD patients, inadequate sAPP-α levels may be sufficient to polarize APP processing towards the amyloidogenic, Aβ-producing route. Therefore, restoration of sAPP-α or enhancement of its association with BACE may be viable strategies to ameliorate imbalances in APP processing that can lead to AD pathogenesis.
