Identification of biomarkers for differential diagnosis of neurodegenerative and non-neurodegenerative dementia

阿尔茨海默病(AD)与其他形式的痴呆症的不同之处在于它与淀粉样β多肽(Aβ_&lt；42&gt；；)有关，后者对神经细胞有毒性作用。这一效应表明Aβ42改变了神经细胞中的蛋白质表达。在本研究中，我们使用小鼠原代培养的神经元，并研究了Aβ_&lt；42&gt；孵育后上清液中蛋白质的变化。鉴于凋亡细胞的外膜上出现了酸性磷脂(磷脂酰丝氨酸，PS)，我们使用PS作为探针，并用蛋白质组学的方法鉴定了PS包裹的磁性纳米珠上的蛋白质。在已鉴定的许多蛋白质中，我们重点研究了参与清除细胞凋亡的膜联蛋白A5和乳脂球-EGF-因子8(MFG-E8)。Aβ_&lt；42&gt；培养上清液中膜联蛋白A5和MFG-E8均显著增加。

Alzheimer's disease(AD) differs from other forms of dementia in its relation to amyloid beta peptide(Aβ_<42>), which has a toxic effect on neuronal cells. This effect implies that protein expression is changed in neuronal cells by Aβ42. In the present study, we used the mice primary culture neurons and investigated the proteins in the supernatant after incubation with or without Aβ_<42>. In view of the appearance of an acidic phospholipid(phosphatidylserine(PS)) on the outer plasma membrane of an apoptotic cell, we used PS as a probe and proteins bound to PS-coated magnetic nano-beads were identified using a proteomic approach. Of a number of proteins identified, we focused on annexin A5 and milk fat globule-EGF-factor 8(MFG-E8) that is involved in the clearance of apoptotic cells. Both annexin A5 and MFG-E8 were found to be increased significantly in the culture supernatant by Aβ_<42>.