S2R modulators tested by several independent groups have been shown to be neuroprotective, be synaptoprotective, block toxic amyloid-β oligomers from binding to neuronal synapses, and restore neuronal functioning and cognitive deficits across various preclinical models, from neurons in culture to in vivo Alzheimer’s disease models from C. elegans to rodents [141]. This evidence concerns the gene TMEM97 and early-onset autosomal dominant Alzheimer disease.