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bioRxiv · 10.1101/2023.10.16.562481

A systematic review and meta-analysis of tau phosphorylation in mouse models of familial Alzheimer's disease

Metaxas, A.·Kourti, M.
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Abstract

BackgroundTransgenic models of familial Alzheimers disease (AD) serve as valuable tools for probing the molecular mechanisms associated with amyloid-beta (A{beta})-induced pathology. Here, we sought to evaluate the levels of phosphorylated tau (p-tau) protein, and explore potential age-related variations in the hyperphosphorylation of tau, in mouse models of cerebral amyloidosis. MethodsThe PubMed and Scopus databases were searched for studies measuring soluble p-tau in 5xFAD, APPswe/PSEN1de9, J20 and APP23 mice. Data were extracted and analyzed using standardized procedures. ResultsFor the 5xFAD model, the search yielded 36 studies eligible for meta-analysis. Levels of p-tau were higher in 5xFAD mice relative to control, a difference that was evident in both the carboxy-terminal (CT) and proline-rich (PR) domains of tau. Age negatively moderated the effects of genotype on CT domain phosphorylated tau, particularly in studies using hybrid mice, female mice, and preparations from the cortex. For the APPswe/PSEN1de9 model, the search yielded 27 studies. Analysis showed tau hyperphosphorylation in transgenic vs. control animals, evident in both the CT and PR regions of tau. Age positively moderated the effects of genotype on PR domain phosphorylated tau in the cortex of APPswe/PSEN1de9 mice. A meta-analysis was not performed for the J20 and APP23 models, due to the limited number of studies measuring p-tau levels in these mice (<10 studies). ConclusionsAlthough tau is hyperphosphorylated in both 5xFAD and APPswe/PSEN1de9 mice, the effects of ageing on p-tau are contingent upon the mouse model being examined. These observations emphasize the importance of tailoring model selection to the appropriate disease stage when assessing the relationship between A{beta} and tau, and suggest that there are optimal intervention points for the administration of both anti-amyloid and anti-tau therapies.

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Metaxas, A., Kourti, M.. 2023-10-17. A systematic review and meta-analysis of tau phosphorylation in mouse models of familial Alzheimer's disease. https://doi.org/10.1101/2023.10.16.562481

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