Alzheimer amyloid protein precursor is localized in nerve terminal preparations to Rab5-containing vesicular organelles distinct from those implicated in the synaptic vesicle pathway.
In order to localize amyloid protein precursor (APP) in nerve terminals, we have immunoisolated vesicular organelles from nerve terminal preparations using antibodies to Rab5 and synaptophysin. These immunoisolates were then analyzed by electron microscopy and by immunoblotting. The synaptophysin immunoisolates represented a nearly homogeneous population of small synaptic vesicles, with less than 10% contamination by other organelles, and very little APP. In contrast, Rab5 immunoisolates contained, in addition to small synaptic vesicles, substantial numbers of large uni- and bilamellar vesicles and high levels of APP. Thus, it appears that nerve terminal APP is contained predominantly in large vesicular organelles, distinct from synaptic vesicles and from the synaptic vesicle recycling pathway.
Ikin
A F
AF
Laboratory of Molecular and Cellular Neurosciences and Zachary and Elizabeth M. Fisher Center, The Rockefeller University, New York, New York 10021, USA.
Annaert
W G
WG
Takei
K
K
De Camilli
P
P
Jahn
R
R
Greengard
P
P
Buxbaum
J D
JD
D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry*; D000818:Animals; D001923:Brain Chemistry; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D013572:Synaptic Vesicles / Q000737:chemistry*; D020696:rab5 GTP-Binding Proteins
D016564:Amyloid beta-Protein Precursor; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins