| First Author | Chiang ACA | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 5 | Pages | 1349-1364 |
| PubMed ID | 29626114 | Mgi Jnum | J:261588 |
| Mgi Id | MGI:6155842 | Doi | 10.1084/jem.20171484 |
| Citation | Chiang ACA, et al. (2018) Combination anti-Abeta treatment maximizes cognitive recovery and rebalances mTOR signaling in APP mice. J Exp Med 215(5):1349-1364 |
| abstractText | Drug development for Alzheimer's disease has endeavored to lower amyloid beta (Abeta) by either blocking production or promoting clearance. The benefit of combining these approaches has been examined in mouse models and shown to improve pathological measures of disease over single treatment; however, the impact on cellular and cognitive functions affected by Abeta has not been tested. We used a controllable APP transgenic mouse model to test whether combining genetic suppression of Abeta production with passive anti-Abeta immunization improved functional outcomes over either treatment alone. Compared with behavior before treatment, arresting further Abeta production (but not passive immunization) was sufficient to stop further decline in spatial learning, working memory, and associative memory, whereas combination treatment reversed each of these impairments. Cognitive improvement coincided with resolution of neuritic dystrophy, restoration of synaptic density surrounding deposits, and reduction of hyperactive mammalian target of rapamycin signaling. Computational modeling corroborated by in vivo microdialysis pointed to the reduction of soluble/exchangeable Abeta as the primary driver of cognitive recovery. |
