Should tau-targeted therapies be redesigned to account for Aβ-tau synergy rather than targeting tau alone?

The abstract suggests that trials directed solely at tau may need reconsideration given the synergistic relationship with Aβ. This raises fundamental questions about optimal therapeutic design and whether combination approaches are necessary for efficacy.

Gap type: open_question Source paper: Synergy between amyloid-β and tau in Alzheimer’s disease. (2020, Nature neuroscience, PMID:32778792)

[“Comparative behavioral and pathological study in 3xTg or 5xFAD x P301S tau mice receiving anti-A\u03b2 therapy alone vs combined A\u03b2+tau therapy for 6 months”, “Combined therapy achieves >=40% reduction in both amyloid plaques (ThS) and tau tangle burden (AT8) vs either monotherapy”, “Cognitive rescue (Morris water maze, novel object recognition) is significantly better in combined arm vs monotherapy”, “Pharmacodynamic markers confirm dual target engagement (CSF A\u03b242 and p-tau181) in combined arm”]