AMYLOID PRECURSOR PROTEIN IS SYNTHESIZED BY RETINAL GANGLION-CELLS, RAPIDLY TRANSPORTED TO THE OPTIC-NERVE PLASMA-MEMBRANE AND NERVE-TERMINALS, AND METABOLIZED

We have investigated the synthesis, axonal transport, and processing o f the beta-amyloid precursor protein (APP) in in vivo rabbit retinal g anglion cells. These CNS neurons connect the retina to the brain via a xons that comprise the optic nerve. APP is synthesized in retinal gang lion cells and is rapidly transported into the optic nerve in small tr ansport vesicles. It is then transferred to the axonal plasma membrane , as well as to the nerve terminals and metabolized with a t1/2 of les s than 5 h. A significant accumulation of C-terminal amyloidogenic or nonamyloidogenic fragments is seen in the optic nerve 5 h after [S-35] -methionine, [S-35]cysteine injection, which disappears by 24 h. The m ajor molecular mass species of APP in the optic nerve is approximately 110 kDa, and is an APP isoform that does not contain a Kunitz proteas e inhibitor domain. Higher molecular mass species containing this sequ ence are seen mostly in the retina. A protease(s) that can potentially cleave APP to generate an amyloidogenic fragment is present in the sa me optic nerve membrane compartment as APP.