Instead of running trials on the basis of a single diagnosis, e.g., AD, or prediagnosis conditions, trials will focus on composite signatures (e.g., BA-eCBome-tau in EOAD; SCFA-2-AG-glia PET in PD) by assaying the fixation of loops: reducing variance; circadian amplitude renewal; phase coherence; executor slowing; and not just one or the other within a composite signature cross-identified feedback loop [163]. This evidence concerns the gene MAPT and Alzheimer disease.