August 11, 2026

@michaelokun

What really resonated with me from today’s University of Florida Grand Rounds by Dr. John Graff-Radford, a Gator alum and now professor at the Mayo Clinic, was the message that baseline tau may matter enormously when we counsel people about who is most likely to benefit from an Alzheimer’s infusion therapy. The donanemab data make this point particularly compelling: in TRAILBLAZER-ALZ 2, the low/medium tau group had about 35% slowing of decline on the iADRS and 36% on the CDR-SB, while the slide Dr. Graff-Radford presented highlighted an even stronger modeled treatment effect at very low tau burden and progressively less benefit as baseline tau increased. The lecanemab data tell a complementary story. In the no/low tau subgroup shown today, 76% of those receiving lecanemab had no CDR-SB decline at 18 months compared with 55% on placebo, and 59% of the treated group remained without decline at 36 months in the open-label extension. These are subgroup and extension data and therefore should not be oversold, but they raise an important possibility: tau may help define the therapeutic window. We may be moving from simply asking, “Does this person have amyloid and qualify for treatment?” to asking, “How far has the biology progressed, and what is the realistic opportunity for benefit?” For me, that is where tau PET, and perhaps eventually more accessible blood-based tau biomarkers, could become especially valuable for shared decision-making. The message is not that these drugs reverse Alzheimer’s disease, but that identifying and treating the right person earlier, when tau burden is still low, may offer the greatest opportunity to meaningfully slow the disease.