The isoforms of the APOE gene are of profound importance regarding the onset of Alzheimer's disease (AD), with APOE2 conferring resistance, APOE3 conferring neutral susceptibility, and APOE4 conferring 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 (GSH), a powerful antioxidant. 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 total APOE proteins extracted from post-mortem brains of APOE2, APOE3, and APOE4 homozygous mice, total Amyloid β (Aβ) protein, and total hyper-phosphorylated Tau (HP-Tau) from mice at 3-, 6-, 9-, and 12-month ages. We found that administration of L-cysteine trends toward lowering levels of Aβ in the APOE3 cohort, but this effect is statistically insignificant. On the other hand, L-cysteine caused a significant increase in APOE4 abundance, but a significant decrease in APOE3 abundance regarding diet [F(6,42) = 5.61, p = 0.01]. Furthermore, administration of L-cysteine revealed trends toward lowering HP-Tau deposition in the APOE2 and APOE3 cohorts, but increasing deposition in the APOE4 cohort, although these effects are statistically insignificant. Moreover, immunohistochemistry analyses on the hippocampus and midsagittal brain revealed no effects of L-cysteine on Aβ. Results also showed a decrease in HP-Tau without regard to APOE genotype, but this was not statistically significant (p = 0.18). Taken together, these data suggest that L-cysteine may serve as a promising intervention for AD pathology, although future studies necessitate increasing statistical power to confirm the effect of diet on Aβ and HP-Tau deposition.
