| First Author | Laversenne V | Year | 2020 |
| Journal | Acta Neuropathol Commun | Volume | 8 |
| Issue | 1 | Pages | 198 |
| PubMed ID | 33225991 | Mgi Jnum | J:348205 |
| Mgi Id | MGI:6800416 | Doi | 10.1186/s40478-020-01069-3 |
| Citation | Laversenne V, et al. (2020) Anti-Abeta antibodies bound to neuritic plaques enhance microglia activity and mitigate tau pathology. Acta Neuropathol Commun 8(1):198 |
| abstractText | The brain pathology of Alzheimer's disease (AD) is characterized by the misfolding and aggregation of both the amyloid beta (Abeta) peptide and hyperphosphorylated forms of the tau protein. Initial Abeta deposition is considered to trigger a sequence of deleterious events contributing to tau pathology, neuroinflammation and ultimately causing the loss of synapses and neurons. To assess the effect of anti-Abeta immunization in this context, we generated a mouse model by overexpressing the human tau protein in the hippocampus of 5xFAD mice. Abeta plaque deposition combined with human tau overexpression leads to an array of pathological manifestations including the formation of tau-positive dystrophic neurites and accumulation of hyperphosphorylated tau at the level of neuritic plaques. Remarkably, the presence of human tau reduces microglial clustering in proximity to the Abeta plaques, which may affect the barrier role of microglia. In this mouse model, continuous administration of anti-Abeta antibodies enhances the clustering of microglial cells even in the presence of tau. Anti-Abeta immunization increases plaque compaction, reduces the spread of tau in the hippocampal formation and prevents the formation of tau-positive dystrophic neurites. However, the treatment does not significantly reduce tau-induced neurodegeneration in the dentate gyrus. These results highlight that anti-Abeta immunization is able to enhance microglial activity around neuritic plaques, mitigating part of the tau-induced pathological manifestations. |
