| First Author | Ganesan K | Year | 2024 |
| Journal | Front Aging Neurosci | Volume | 16 |
| Pages | 1357405 | PubMed ID | 38476659 |
| Mgi Jnum | J:348994 | Mgi Id | MGI:7612858 |
| Doi | 10.3389/fnagi.2024.1357405 | Citation | Ganesan K, et al. (2024) Modeling sporadic Alzheimer's disease in mice by combining Apolipoprotein E4 risk gene with environmental risk factors. Front Aging Neurosci 16:1357405 |
| abstractText | INTRODUCTION: Developing effective treatment for Alzheimer's disease (AD) remains a challenge. This can be partially attributed to the fact that the mouse models used in preclinical research largely replicate familial form of AD, while majority of human cases are sporadic; both forms differ widely in the onset and origin of pathology, therefore requiring specific/targeted treatments. METHODS: In this study, we aimed to model sporadic AD in mice by combining two of the many risk factors that are strongly implicated in AD: ApoE4, a major genetic risk factor, together with an inflammatory stimuli. Accordingly, we subjected ApoE4 knock in (KI) mice, expressing humanized ApoE4, to low doses of Lipopolysaccharide (LPS) injections (i.p, weekly, for 4 months). RESULTS: We assessed these animals for behavioral impairments at 6 months of age using Open Field, Y-maze, and Barnes Maze Test. LPS induced hypoactivity was observed in the Open Field and Y-maze test, whereas spatial learning and memory was intact. We then quantified differences in dendritic spine density, which is a strong correlate of AD. ApoE4KI mice showed a significant reduction in the number of spines after treatment with LPS, whereas there were no obvious differences in the total number of microglia and astrocytes. DISCUSSION: To conclude, in the current study the APoEe4 risk gene increases the vulnerability of hippocampal neurons to inflammation induced spine loss, laying a foundation for an early sporadic AD mouse model. |
