| First Author | Farfara D | Year | 2023 |
| Journal | J Neuroinflammation | Volume | 20 |
| Issue | 1 | Pages | 174 |
| PubMed ID | 37496076 | Mgi Jnum | J:338543 |
| Mgi Id | MGI:7513340 | Doi | 10.1186/s12974-023-02823-9 |
| Citation | Farfara D, et al. (2023) Physiological expression of mutated TAU impaired astrocyte activity and exacerbates beta-amyloid pathology in 5xFAD mice. J Neuroinflammation 20(1):174 |
| abstractText | BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia in the world. The pathology of AD is affiliated with the elevation of both tau (tau) and beta-amyloid (Abeta) pathologies. Yet, the direct link between natural tau expression on glia cell activity and Abeta remains unclear. While experiments in mouse models suggest that an increase in Abeta exacerbates tau pathology when expressed under a neuronal promoter, brain pathology from AD patients suggests an appearance of tau pathology in regions without Abeta. METHODS: Here, we aimed to assess the link between tau and Abeta using a new mouse model that was generated by crossing a mouse model that expresses two human mutations of the human MAPT under a mouse Tau natural promoter with 5xFAD mice that express human mutated APP and PS1 in neurons. RESULTS: The new mouse model, called 5xFAD TAU, shows accelerated cognitive impairment at 2 months of age, increased number of Abeta depositions at 4 months and neuritic plaques at 6 months of age. An expression of human mutated TAU in astrocytes leads to a dystrophic appearance and reduces their ability to engulf Abeta, which leads to an increased brain Abeta load. Astrocytes expressing mutated human TAU showed an impairment in the expression of vascular endothelial growth factor (VEGF) that has previously been suggested to play an important role in supporting neurons. CONCLUSIONS: Our results suggest the role of tau in exacerbating Abeta pathology in addition to pointing out the potential role of astrocytes in disease progression. Further research of the crosstalk between tau and Abeta in astrocytes may increase our understanding of the role glia cells have in the pathology of AD with the aim of identifying novel therapeutic interventions to an otherwise currently incurable disease. |
