| First Author | He Y | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 1193 |
| PubMed ID | 30867420 | Mgi Jnum | J:273276 |
| Mgi Id | MGI:6286795 | Doi | 10.1038/s41467-019-09114-z |
| Citation | He Y, et al. (2019) Amyloid beta oligomers suppress excitatory transmitter release via presynaptic depletion of phosphatidylinositol-4,5-bisphosphate. Nat Commun 10(1):1193 |
| abstractText | Amyloid beta (Abeta) oligomer-induced aberrant neurotransmitter release is proposed to be a crucial early event leading to synapse dysfunction in Alzheimer's disease (AD). In the present study, we report that the release probability (Pr) at the synapse between the Schaffer collateral (SC) and CA1 pyramidal neurons is significantly reduced at an early stage in mouse models of AD with elevated Abeta production. High nanomolar synthetic oligomeric Abeta42 also suppresses Pr at the SC-CA1 synapse in wild-type mice. This Abeta-induced suppression of Pr is mainly due to an mGluR5-mediated depletion of phosphatidylinositol-4,5-bisphosphate (PIP2) in axons. Selectively inhibiting Abeta-induced PIP2 hydrolysis in the CA3 region of the hippocampus strongly prevents oligomeric Abeta-induced suppression of Pr at the SC-CA1 synapse and rescues synaptic and spatial learning and memory deficits in APP/PS1 mice. These results first reveal the presynaptic mGluR5-PIP2 pathway whereby oligomeric Abeta induces early synaptic deficits in AD. |
