| First Author | Savas JN | Year | 2017 |
| Journal | Cell Rep | Volume | 21 |
| Issue | 9 | Pages | 2614-2627 |
| PubMed ID | 29186695 | Mgi Jnum | J:255230 |
| Mgi Id | MGI:6104105 | Doi | 10.1016/j.celrep.2017.11.009 |
| Citation | Savas JN, et al. (2017) Amyloid Accumulation Drives Proteome-wide Alterations in Mouse Models of Alzheimer's Disease-like Pathology. Cell Rep 21(9):2614-2627 |
| abstractText | Amyloid beta (Abeta) peptides impair multiple cellular pathways and play a causative role in Alzheimer''s disease (AD) pathology, but how the brain proteome is remodeled by this process is unknown. To identify protein networks associated with AD-like pathology, we performed global quantitative proteomic analysis in three mouse models at young and old ages. Our analysis revealed a robust increase in Apolipoprotein E (ApoE) levels in nearly all brain regions with increased Abeta levels. Taken together with prior findings on ApoE driving Abeta accumulation, this analysis points to a pathological dysregulation of the ApoE-Abeta axis. We also found dysregulation of protein networks involved in excitatory synaptic transmission. Analysis of the AMPA receptor (AMPAR) complex revealed specific loss of TARPgamma-2, a key AMPAR-trafficking protein. Expression of TARPgamma-2 in hAPP transgenic mice restored AMPA currents. This proteomic database represents a resource for the identification of protein alterations responsible for AD. |
