(1) AD axons display predominant amphisome accumulation and reduced retrograde transport of LEs/amphisomes (Figure 2 and Figure 2—figure supplement 1); (2) Expression Snapin, but not its dynein-binding defective mutant, significantly reduces AV retention by enhancing their retrograde transport in AD axons (Figure 7); (3) Snapin-enhanced AV transport rescues AV accumulation in AD axons upon autophagy induction (Figure 7—figure supplement 1); and (4) deleting Snapin recapitulates AD-associated autophagic stress in distal axons (Figure 6 and Figure 6—figure supplement 1). The gene discussed is SNAPIN; the disease is Alzheimer disease.