Figure 4. Methionine and choline supplementation reduce Aβ proteotoxic effects in B₁₂-deficient animals.

(A) Schematic diagram shows link between the vitamin-B₁₂-dependent methionine/SAMe cycle (blue) and phospholipid biosynthesis. SAH, s-adenosyl-l-homocysteine; PE, phosphoethanolamine; PC, phosphocholine; PtdCho, phosphatidylcholine. PtdCho can be synthesized from choline or methylation of PE.

(B) Aβ animals grown on OP50 had higher levels of Hcy compared to those raised on HB101- or B₁₂-supplemented plates (n = 4).

(C) Supplementation with 15 mM Hcy accelerated paralysis of Aβ animals grown on both OP50 and HB101 but did not eliminate the dietary shift (n ≥ 105).

(D) Supplementation with 13.4 mM L-methionine eliminated the diet-induced shift in paralysis (n ≥ 116).

(E) Methionine supplementation (67 mM) delayed Aβ-induced paralysis in the metr-1 mutant (n ≥ 67).

(F) Supplementation of the metr-1 mutant with 13.4 mM and 67 mM methionine delayed the median time to Aβ-induced paralysis (n ≥ 3).

(G) Supplementation with 67 mM methionine caused a significant increase in ATP in the metr-1 mutant (n ≥ 4).

(H) Supplementation with 10 mM choline eliminated the impact of bacterial diet on Aβ-induced paralysis (n ≥ 107).

(I) Choline concentration above 10 mM had no additional protective effect (n ≥ 3).

Error bars show SEM; *p < 0.05, **p < 0.01, and ***p < 0.001, one-way ANOVA with Dunnett’s post-test. See also Figure S4.