Apolipoprotein e3 as a risk factor for Alzheimer's disease under conditions of nutritional imbalance.
The presence of one or more copies of the E4 allele of apolipoprotein E (ApoE) is strongly associated with of Alzheimer's disease (AD). The impact of E4 on neurodegeneration is potentiated by dietary oxidative challenge. Our prior studies in transgenic mice demonstrate that, in the face of dietary oxidative challenge, E3 does not provide any further protection than E4 or lack of murine ApoE for aggression, oxidative damage, presenilin-1 expression, and gamma-secretase activity, and provides only partial reduction in phospho-tau levels. Extrapolation of these findings to the human condition leads us to hypothesize that the E3 allele may not provide sufficient neuroprotection under conditions of dietary compromise and/or oxidative challenge. Epidemiological evidence is consistent with this possibility. The E3 allele is approximately half as effective compared to E2 at buffering the impact of a single E4 allele. In addition, the risk of AD increases linearly for the genotypes E2/2, E2/3, and E3/3. It has been proposed that that clinical manifestation of AD may in some cases require the convergence of 2 or more risk factors. We hypothesize that the combined impact of dietary oxidative stress and either the ApoE3 or E4 genotype represents one such condition.
Chan
Amy
A
Center for Cellular Neurobiology and Neurodegeneration Research, UMassLowell, Lowell, MA, USA.
Shea
Thomas B
TB
D000544:Alzheimer Disease / Q000209:etiology* / Q000235:genetics* / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D000818:Animals; D053318:Apolipoprotein E3 / Q000172:deficiency / Q000235:genetics*; D004195:Disease Models, Animal; D006801:Humans; D044342:Malnutrition / Q000150:complications* / Q000235:genetics; D051379:Mice; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D053764:Presenilin-1 / Q000378:metabolism; D012307:Risk Factors; D016875:tau Proteins / Q000378:metabolism
D053318:Apolipoprotein E3; C508853:PSEN1 protein, human; D053764:Presenilin-1; D016875:tau Proteins; D053829:Amyloid Precursor Protein Secretases