Affiliations: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA
Correspondence:
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Correspondence to: Dr. Michael D. Greicius, MD, Wu Tsai Neurosciences Institute, 290 Jane Stanford Way, Stanford, CA 94305-5090, USA. Tel.: +1 650 498 4624; E-mail: [email protected].
Abstract: With the FDA approval of aducanumab and lecanemab, and with the recent statistically significant phase 3 clinical trial for donanemab, there is growing enthusiasm for anti-amyloid antibodies in the treatment of Alzheimer’s disease. Here, we discuss three substantial limitations regarding recent anti-amyloid clinical trials: 1) there is little evidence that amyloid reduction correlates with clinical outcome, 2) the reported efficacy of anti-amyloid therapies may be explained by functional unblinding, and 3) donanemab had no effect on tau burden in its phase 3 trial. Taken together, these observations call into question the efficacy of anti-amyloid therapies.
Keywords: Alzheimer’s disease, amyloid, clinical trials, tau
