In Reply Granzotto and Sensi hypothesize that the potential beneficial effects of minocycline in Alzheimer disease in our trial1 may have been obscured by the inhibition of matrix metalloproteinase-9 activation of brain-derived neurotrophic factor (BDNF). Unfortunately, we did not save blood samples from participants that might have allowed us to test whether BDNF levels were reduced in those receiving minocycline. Of course, even if we had evidence that activated BDNF levels were reduced by minocycline in the trial, this would not necessarily explain the lack of minocycline’s efficacy in modifying Alzheimer progression.
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Howard R, Gray R. Minocycline—A Lesson From a Failure—Reply. JAMA Neurol. 2020;77(8):1038. doi:10.1001/jamaneurol.2020.1157
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