| First Author | Chabrier MA | Year | 2012 |
| Journal | J Neurosci | Volume | 32 |
| Issue | 48 | Pages | 17345-50 |
| PubMed ID | 23197725 | Mgi Jnum | J:193050 |
| Mgi Id | MGI:5467463 | Doi | 10.1523/JNEUROSCI.0172-12.2012 |
| Citation | Chabrier MA, et al. (2012) Soluble abeta promotes wild-type tau pathology in vivo. J Neurosci 32(48):17345-50 |
| abstractText | Growing evidence suggests that soluble Abeta species can drive Alzheimer disease (AD) pathogenesis by inducing a cascade of events including tau hyperphosphorylation, proteasome impairment, and synaptic dysfunction. However, these studies have relied largely on in vitro approaches to examine the role of soluble Abeta in AD. In particular, it remains unknown whether soluble Abeta oligomers can facilitate the development of human wild-type tau pathology in vivo. To address this question, we developed a novel transgenic model that expresses low levels of APP with the Arctic familial AD mutation to enhance soluble Abeta oligomer formation in conjunction with wild-type human tau. Using a genetic approach, we show that reduction of beta-site APP cleaving enzyme (BACE) in these ArcTau mice decreases soluble Abeta oligomers, rescues cognition, and, more importantly, reduces tau accumulation and phosphorylation. Notably, BACE reduction decreases the postsynaptic mislocalization of tau in ArcTau mice and reduces the association between NMDA receptors and PSD-95. These studies provide critical in vivo evidence for a strong mechanistic link between soluble Abeta, wild-type tau, and synaptic pathology. |
