In our hibernating animal models, we observed reversible phosphorylation at several of these same residues without detectable tau aggregation, suggesting that while phosphorylation can be sufficient under defined experimental conditions and likely also in AD, its capacity to trigger filament formation in vivo may still depend on additional factors not present in hibernation, such as the very long duration of asymptomatic and symptomatic duration of AD, altered clearance, or local biochemical milieu. Here, MAPT is linked to Alzheimer disease.