| First Author | Welikovitch LA | Year | 2024 |
| Journal | Brain | PubMed ID | 39504519 |
| Mgi Jnum | J:359514 | Mgi Id | MGI:7787281 |
| Doi | 10.1093/brain/awae345 | Citation | Welikovitch LA, et al. (2024) Tau, synapse loss and gliosis progress in an Alzheimer's mouse model after amyloid-beta immunotherapy. Brain |
| abstractText | While preclinical studies assessing drugs for Alzheimer's disease (AD) are conducted in animal models that usually display only one neuropathological feature of AD, patients present with a complex combination of comorbidities and neuropathologies. Importantly, it is well-established that amyloid (Abeta) plaque and tau tangle accumulation interact in a phase-dependent manner, making it difficult to predict how targeting one might influence the other, as well as downstream degeneration. We developed a transgenic mouse model, APP/PS1xTau22, with progressive cortical Abeta deposition and hippocampal tau neurofibrillary inclusions to investigate how both neuropathologies act jointly to bring about neural degeneration, synapse loss, and glial phenotypes. We then assessed whether applying murine chimeric Aducanumab, an anti-amyloid immunotherapy, could impact the synergistic relationship between amyloid and tau. Drug treatment resulted in a approximately 70% reduction in Abeta deposition in hippocampal and cortical areas and produced a robust peri-plaque microglial and astrocytic response. Removing amyloid from the brain did not reverse or slow tau pathology or alter synapse loss. Our findings suggest that, once the interaction between amyloid and tau is set in motion, reducing plaque burden by Abeta immunotherapy may stimulate glial responses, but is insufficient to curb degenerative phenotypes in this model. |
