Plasmalogens improve swimming performance by modulating the expression of genes involved in amino acid and lipid metabolism, oxidative stress, and ferroptosis in an Alzheimer's disease zebrafish model

Plasmalogens (PLs) are critical to human health. Studies have reported a link between the downregulation of PLs levels and cognitive impairments in patients with Alzheimer's disease (AD). However, the underlying mechanisms remain to be clarified. In the present study, an AlCl3-induced AD zebrafish model was established, and the model was used to elucidate the neuroprotective effects of PLs on AD by analysing the transcriptional profiles of zebrafish in the control, AD model, AD_PL, and PL groups. Chronic AlCl3 exposure caused swimming performance impairments in the zebrafish, yet PLs supplementation could improve the dyskinesia recovery rate in the AD zebrafish model. Through transcriptional profiling, a total of 5413 statistically significant differentially expressed genes (DEGs) were identified among the groups. In addition to the DEGs involved in amino acid metabolism, we found that the genes related to iron homeostasis, lipid peroxidation, and oxidative stress, all of which contribute to ferroptosis, were dramatically altered among different groups. These results suggest that seafood-derived PLs, in addition to their role in eliminating oxidative stress, can improve the swimming performance in AlCl3-exposed zebrafish partly by suppressing neuronal ferroptosis and accelerating synaptic transmission at the transcriptional level. This study provides evidence for PLs to be developed as a functional food supplement to relieve AD symptoms.