| First Author | Wu Z | Year | 2020 |
| Journal | Cell Death Dis | Volume | 11 |
| Issue | 12 | Pages | 1058 |
| PubMed ID | 33311478 | Mgi Jnum | J:306682 |
| Mgi Id | MGI:6706185 | Doi | 10.1038/s41419-020-03270-7 |
| Citation | Wu Z, et al. (2020) Delta-secretase triggers Alzheimer's disease pathologies in wild-type hAPP/hMAPT double transgenic mice. Cell Death Dis 11(12):1058 |
| abstractText | Alzheimer's disease (AD) is the most common neurodegenerative disease with multifactorial pathologies including Abeta containing senile plaques and neurofibrillary tangles (NFT) consisted of aggregated Tau. Most of the AD patients are sporadic and the familial mutation hereditary patients are composed only 1% of all cases. However, the current AD mouse models employ mutated APP, PS1, or even Tau mutant, in order to display a portion of AD pathologies. Delta-secretase (legumain, or asparaginyl endopeptidase, AEP) simultaneously cleaves both APP and Tau and augments Abeta production and Tau hyperphosphorylation and aggregation, contributing to AD pathogenesis. Here we show that delta-secretase is sufficient to promote prominent AD pathologies in wild-type hAPP/hMAPT double transgenic mice. We crossed hAPP l5 mice and hMAPT mice to generate double transgenic mouse model carrying both human wild-type APP and Tau. Compared to the single transgenic parents, these double transgenic mice demonstrated AD-related pathologies in one-year-old hAPP/hMAPT mice. Notably, overexpression of delta-secretase in hAPP/hMAPT double-transgenic mice evidently accelerated enormous senile plaques and NFT, associated with prominent synaptic defects and cognitive deficits. Hence, delta-secretase facilitates AD pathogenesis independent of any patient-derived mutation. |
