| First Author | Aladeokin AC | Year | 2019 |
| Journal | Neurobiol Dis | Volume | 132 |
| Pages | 104603 | PubMed ID | 31494281 |
| Mgi Jnum | J:282586 | Mgi Id | MGI:6381849 |
| Doi | 10.1016/j.nbd.2019.104603 | Citation | Aladeokin AC, et al. (2019) Network-guided analysis of hippocampal proteome identifies novel proteins that colocalize with Abeta in a mice model of early-stage Alzheimer's disease. Neurobiol Dis 132:104603 |
| abstractText | Alzheimer's disease (AD) is an incurable neurodegenerative disease characterized by memory loss and neurotoxic amyloid beta (Abeta) plaques accumulation. Numerous pharmacological interventions targeting Abeta plaques accumulation have failed to alleviate AD. Also, the pathological alterations in AD start years before the onset of clinical symptoms. To identify proteins at play during the early stage of AD, we conducted proteomic analysis of the hippocampus of young App(NL-F) mice model of AD at the preclinical phase of the disease. This was followed by interactome ranking of the proteome into hubs that were further validated in vivo using immunoblot analysis. We also performed double-immunolabeling of these hub proteins and Abeta to quantify colocalization. Behavioral analysis revealed no significant difference in memory performance between 8-month-old App(NL-F) and control mice. The upregulation and downregulation of several proteins were observed in the App(NL-F) mice compared to control. These proteins corresponded to pathways and processes related to Abeta clearance, inflammatory-immune response, transport, mitochondrial metabolism, and glial cell proliferation. Interactome analysis revealed several proteins including DLGP5, DDX49, CCDC85A, ADCY6, HEPACAM, HCN3, PPT1 and TNPO1 as essential proteins in the App(NL-F) interactome. Validation by immunoblot confirmed the over-expression of these proteins except HCN3 in the early-stage AD mice hippocampus. Immunolabeling revealed a significant increase in ADCY6/Abeta and HEPACAM/Abeta colocalized puncta in App(NL-F) mice compared to WT. These data suggest that these proteins may be involved in the early stage of AD. Our work suggests new targets and biomarkers for AD diagnosis and therapeutic intervention. |
