| First Author | Chen XQ | Year | 2023 |
| Journal | Alzheimers Dement | Volume | 19 |
| Issue | 5 | Pages | 2095-2116 |
| PubMed ID | 36370135 | Mgi Jnum | J:351610 |
| Mgi Id | MGI:7702377 | Doi | 10.1002/alz.12835 |
| Citation | Chen XQ, et al. (2023) Reduced synaptic proteins and SNARE complexes in Down syndrome with Alzheimer's disease and the Dp16 mouse Down syndrome model: Impact of APP gene dose. Alzheimers Dement 19(5):2095-2116 |
| abstractText | INTRODUCTION: Synaptic failure, a hallmark of Alzheimer's disease (AD), is correlated with reduced levels of synaptic proteins. Though people with Down syndrome (DS) are at markedly increased risk for AD (AD-DS), few studies have addressed synapse dysfunction. METHODS: Synaptic proteins were measured in the frontal cortex of DS, AD-DS, sporadic AD cases, and controls. The same proteins were examined in the Dp16 model of DS. RESULTS: A common subset of synaptic proteins were reduced in AD and AD-DS, but not in DS or a case of partial trisomy 21 lacking triplication of APP gene. Pointing to compromised synaptic function, the reductions in AD and AD-DS were correlated with reduced SNARE complexes. In Dp16 mice reductions in syntaxin 1A, SNAP25 and the SNARE complex recapitulated findings in AD-DS; reductions were impacted by both age and increased App gene dose. DISCUSSION: Synaptic phenotypes shared between AD-DS and AD point to shared pathogenetic mechanisms. |
