| First Author | Sawa M | Year | 2022 |
| Journal | Alzheimers Dement | Volume | 18 |
| Issue | 6 | Pages | 1203-1234 |
| PubMed ID | 34757693 | Mgi Jnum | J:351605 |
| Mgi Id | MGI:7702370 | Doi | 10.1002/alz.12463 |
| Citation | Sawa M, et al. (2022) Impact of increased APP gene dose in Down syndrome and the Dp16 mouse model. Alzheimers Dement 18(6):1203-1234 |
| abstractText | INTRODUCTION: People with Down syndrome (DS) are predisposed to Alzheimer's disease (AD). The amyloid hypothesis informs studies of AD. In AD-DS, but not sporadic AD, increased APP copy number is necessary, defining the APP gene dose hypothesis. Which amyloid precursor protein (APP) products contribute needs to be determined. METHODS: Brain levels of full-length protein (fl-hAPP), C-terminal fragments (hCTFs), and amyloid beta (Abeta) peptides were measured in DS, AD-DS, non-demented controls (ND), and sporadic AD cases. The APP gene-dose hypothesis was evaluated in the Dp16 model. RESULTS: DS and AD-DS differed from ND and AD for all APP products. In AD-DS, Abeta42 and Abeta40 levels exceeded AD. APP products were increased in the Dp16 model; increased APP gene dose was necessary for loss of vulnerable neurons, tau pathology, and activation of astrocytes and microglia. DISCUSSION: Increases in APP products other than Abeta distinguished AD-DS from AD. Deciphering AD-DS pathogenesis necessitates deciphering which APP products contribute and how. |
