Differential regulation of APP secretion by apolipoprotein E3 and E4.
The apolipoprotein E isozyme, apolipoprotein E4, has been implicated as a risk factor for Alzheimer's disease. One reason for the increased risk may be that apolipoprotein E binds to the A beta peptide, but there may be other factors as well. We show that apolipoprotein E is a potent regulator of the secretion of amyloid precursor protein. In cultures of PC12 cells, nanomolar levels of apolipoprotein E3 induce a rapid decrease in the secretion of APP, being observable in 30 min. and stable over 24 hours. Apolipoprotein E4, in contrast, increases secretion of APP over a similar time course. Reciprocal changes occur in cellular amyloid precursor protein. Differential characteristics are also seen in apo E binding to the cells, where apo E4 binds over a slower time course than apo E3. These results suggest a novel mechanism by which apolipoprotein E may be influencing the metabolism of amyloid precursor protein.
Wolozin
B L
BL
Section on Geriatric Psychiatry, NIMH, Bethesda, Maryland 20892, USA. ben@codon.nih.gov
Basaric-Keys
J
J
Canter
R
R
Li
Y
Y
Vanderputten
D
D
Sunderland
T
T
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000502:physiology*; D016716:PC12 Cells / Q000378:metabolism; D051381:Rats; D013997:Time Factors
D016564:Amyloid beta-Protein Precursor; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E