TY - JOUR
T1 - Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport
AU - Koo, Edward H.
AU - Sisodia, Sangram S.
AU - Archer, David R.
AU - Martin, Lee J.
AU - Weidemann, Andreas
AU - Beyreuther, Konrad
AU - Fischer, Peter
AU - Masters, Colin L.
AU - Price, Donald L.
PY - 1990
Y1 - 1990
N2 - In the brains of aged humans and cases of Alzheimer disease, deposits of amyloid in senile plaques are located in proximity to nerve processes. The principal component of this extracellular amyloid is β/A4, a peptide derived from a larger amyloid precursor protein (APP), which is actively expressed in brain and systemic organs. Mechanisms that result in the proteolysis of APP to form β/A4, previously termed β-amyloid protein, and the subsequent deposition of the peptide in brain are unknown. If β/A4 in senile plaques is derived from neuronally synthesized APP and deposited at locations remote from sites of synthesis, then APP must be transported from neuronal cell bodies to distal nerve processes in proximity to deposits of amyloid. In this study, using several immunodetection methods, we demonstrate that APP is transported axonally in neurons of the rat peripheral nervous system. Moreover, our investigations show that APP is transported by means of the fast anterograde component. These findings are consistent with the hypothesis of a neuronal origin of β/A4, in which amyloid is deposited in the brain parenchyma of aged individuals and cases of Alzheimer disease. In this setting, we suggest that APP is synthesized in neurons and delivered to dystrophic nerve endings, where subsequent alterations of local processing of APP result in deposits of brain amyloid.
AB - In the brains of aged humans and cases of Alzheimer disease, deposits of amyloid in senile plaques are located in proximity to nerve processes. The principal component of this extracellular amyloid is β/A4, a peptide derived from a larger amyloid precursor protein (APP), which is actively expressed in brain and systemic organs. Mechanisms that result in the proteolysis of APP to form β/A4, previously termed β-amyloid protein, and the subsequent deposition of the peptide in brain are unknown. If β/A4 in senile plaques is derived from neuronally synthesized APP and deposited at locations remote from sites of synthesis, then APP must be transported from neuronal cell bodies to distal nerve processes in proximity to deposits of amyloid. In this study, using several immunodetection methods, we demonstrate that APP is transported axonally in neurons of the rat peripheral nervous system. Moreover, our investigations show that APP is transported by means of the fast anterograde component. These findings are consistent with the hypothesis of a neuronal origin of β/A4, in which amyloid is deposited in the brain parenchyma of aged individuals and cases of Alzheimer disease. In this setting, we suggest that APP is synthesized in neurons and delivered to dystrophic nerve endings, where subsequent alterations of local processing of APP result in deposits of brain amyloid.
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U2 - 10.1073/pnas.87.4.1561
DO - 10.1073/pnas.87.4.1561
M3 - Article
C2 - 1689489
AN - SCOPUS:0025056563
SN - 0027-8424
VL - 87
SP - 1561
EP - 1565
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 4
ER -