Together, our findings indicate that the “loosening” or “tightening” of axonal MAMs impacts Aβ generation and mitochondrial mobility in AD neurons (Figure 6), which is consistent with our previous report demonstrating that the inactivation of S1R downregulated axonal MAM assembly and resulted in a severe reduction in axonal Aβ levels.9 This evidence concerns the gene TMBIM4 and Alzheimer disease.