| First Author | Steffen J | Year | 2017 |
| Journal | Acta Neuropathol Commun | Volume | 5 |
| Issue | 1 | Pages | 49 |
| PubMed ID | 28637503 | Mgi Jnum | J:312842 |
| Mgi Id | MGI:6791758 | Doi | 10.1186/s40478-017-0448-2 |
| Citation | Steffen J, et al. (2017) Expression of endogenous mouse APP modulates beta-amyloid deposition in hAPP-transgenic mice. Acta Neuropathol Commun 5(1):49 |
| abstractText | Amyloid-beta (Abeta) deposition is one of the hallmarks of the amyloid hypothesis in Alzheimer's disease (AD). Mouse models using APP-transgene overexpression to generate amyloid plaques have shown to model only certain parts of the disease. The extent to which the data from mice can be transferred to man remains controversial. Several studies have shown convincing treatment results in reducing Abeta and enhancing cognition in mice but failed totally in human. One model-dependent factor has so far been almost completely neglected: the endogenous expression of mouse APP and its effects on the transgenic models and the readout for therapeutic approaches.Here, we report that hAPP-transgenic models of amyloidosis devoid of endogenous mouse APP expression (mAPP-knockout / mAPPko) show increased amounts and higher speed of Abeta deposition than controls with mAPP. The number of senile plaques and the level of aggregated hAbeta were elevated in mAPPko mice, while the deposition in cortical blood vessels was delayed, indicating an alteration in the general aggregation propensity of hAbeta together with endogenous mAbeta. Furthermore, the cellular response to Abeta deposition was modulated: mAPPko mice developed a pronounced and age-dependent astrogliosis, while microglial association to amyloid plaques was diminished. The expression of human and murine aggregation-prone proteins with differing amino acid sequences within the same mouse model might not only alter the extent of deposition but also modulate the route of pathogenesis, and thus, decisively influence the study outcome, especially in translational research. |
