南佛羅里達(dá)大學(xué)精神病學(xué)和行為神經(jīng)科學(xué)系研究小組發(fā)現(xiàn)淀粉樣前體蛋白（APP）片段——SAPP-α與阿爾茨海默氏癥有關(guān),。SAPP-α似乎能調(diào)控自己的生產(chǎn)。這一發(fā)現(xiàn)對(duì)通過調(diào)控APP預(yù)防或治療阿爾茨海默氏癥具有重要意義,。
相關(guān)研究結(jié)果發(fā)表于今天的Nature Communications雜志上,。
全世界估計(jì)有30萬人阿爾茨海默氏癥，而在美國這一人數(shù)為5萬,。隨著“嬰兒潮”一代的老齡化,，在美國因年齡增長(zhǎng)導(dǎo)致的疾病的患病率預(yù)計(jì)在未來幾年大幅增加。目前,，有沒有積極的疾病預(yù)防,、治療手段能扭轉(zhuǎn)或阻止阿爾茨海默氏病。
論文主要作者、USF衛(wèi)生署的精神病學(xué)和行為神經(jīng)科學(xué)Demian Obregon博士說：阿爾茨海默氏癥相關(guān)的危險(xiǎn)因素導(dǎo)致SAPP-α水平下降,，從而導(dǎo)致Aβ的形成過程中一種關(guān)鍵酶過度活躍,。
在細(xì)胞實(shí)驗(yàn)初步研究以及后續(xù)使用阿爾茨海默氏病的基因工程小鼠的研究中，研究人員發(fā)現(xiàn),，中和SAPP-α能增強(qiáng)Aβ的形成,。SAPP-α的這種活性功能依賴于SAPP-α與APP轉(zhuǎn)換酶（BACE1）之間發(fā)生作用的功能。當(dāng)這種SAPP-α與APP轉(zhuǎn)換酶之間的互動(dòng)被打破時(shí),，Aβ的形成會(huì)恢復(fù)到正常水平,。
作者認(rèn)為通過監(jiān)測(cè)和糾正SAPP-α的低水平或通過加強(qiáng)SAPP-α與BACE的相互作用，將來老年癡呆癥或可預(yù)防和治療,。（生物谷：Bioon）
doi:10.1038/ncomms1781
PMC:
PMID:
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.
