In a recently published study, TREM2 deletion was found to exacerbate tau pathology and promote brain atrophy in a mouse model that overexpressed human tau with the P301L mutation and human amyloid precursor protein (APP) but had no effect in a model that solely overexpressed mutant tau, suggesting that TREM2 function is neither protective nor detrimental in a pure tauopathy setting [14]. Here, APP is linked to tauopathy.