Differential Regulation of APP Secretion by Apolipoprotein E3 and E4a

Abstract

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.

Small heat shock proteins inhibit in vitro Aβ1–42 amyloidogenesis

“…It is important to stress that several other proteins, including apolipoproteins E and J (apoE and apoJ) and transthyretin, have been implicated in modulating amyloid formation or function. Distinct alleles of apoE have been reported to inhibit (apoE3) or promote (apoE4) amyloid formation, possibly by influencing the rate of APP secretion [38]. ApoJ, a widely distributed protein, inhibits toxicity of Aβ 1–40 in vitro [39].…”

Flavonoids and fibrate modulate apoE4-induced processing of amyloid precursor protein in neuroblastoma cells

“…The increase in intracellular fl-APP was not due to the effect of apoE4 on APP transgene expression or mRNA stability, as confirmed by the qRT-PCR experiment. This indicates that apoE4 affected post-translational processing of APP ( Wolozin et al, 1996 ).…”