A Tale of Two Mice: Altered TREM2 Signalling Contributes to the Disparate Alzheimer's Disease Pathological Phenotypes Observed in ABI3‐Deficient Transgenic CRND8 and 5XFAD mice

We have demonstrated that TREM2 signalling and the related AD-associated functions are significantly altered in SJL microglia. In addition, previous co-expression network analyses have suggested a close functional relationship between TREM2 and ABI3. A combined presence of altered TREM2 signalling and ABI3 deletion may explain the diverging phenotypes observed in TgCRND8 and 5XFAD mouse models. We are currently investigating other potential contributing factors such as differences in genetic background and AD transgenes expressed in these mouse models. We aim to uncover the molecular machinery that links TREM2 to ABI3 in microglia and to understand the impact of ABI3 S209F mutation on TREM2 signalling in microglia and in AD pathology, pathing the way towards identifying novel therapeutics.