The APOE gene is of profound importance regarding the onset of Alzheimer's disease (AD). From the small physical differences among the protein products of the isoforms of this gene arises a profound difference in their physiologies. For example, the APOE2 isoform confers resistance to AD, the APOE3 isoform confers neutral susceptibility to AD, and the APOE4 isoform confers proneness to AD. L-cysteine is an amino acid that has several anti-AD properties, among which are its ability to sequester iron and form glutathione – a powerful antioxidant – and therefore may be a promising potential dietary supplement for ameliorating AD pathology. In our experiment, we fed Mus musculus (mice) homozygous for APOE2, APOE3, and APOE4 either a control diet or a diet high in L-cysteine. Using Western blotting analysis, we quantified Amyloid β (Aβ), hyper-phosphorylated Tau (HP-Tau), and the three APOE proteins that we extracted from post-mortem brains of APOE2, APOE3, and APOE4 homozygous mice of 3-, 6-, 9-, and 12-month ages. We calculated a three-way ANOVA on a sample of 86 mice to examine the effect of age, genotype, and diet on protein quantities. We found that administration of L-cysteine trends towards lowering levels of Aβ in each cohort, but this effect is statistically insignificant. On the other hand, L-cysteine caused a significant decrease in APOE production with regard to diet [F(1,62) = 6.17, p=0.02], indicating that less APOE is produced due to the decrease in Aβ burden. Furthermore, administration of L-cysteine revealed no significant impact on or trends regarding HP-Tau deposition between diet types for each cohort. However, we observed that L-cysteine appeared to nullify the increasing trend in HP-Tau deposition between APOE2 and APOE4 cohorts. Thus, L-cysteine may be weakly affecting HP-Tau deposition via its ability to somewhat reduce Aβ burden and consequently prevent the shutdown of the proteosomes responsible for the degradation and clearance of HP-Tau. Taken together, these data suggest that L-cysteine should be considered as an intervention for AD pathology.



College and Department

Life Sciences; Physiology and Developmental Biology



Date Submitted


Document Type





alzheimer's disease, APOE4, APOE3, APOE2, amyloid β, tau, L-cysteine, diet



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Physiology Commons