Dietary synergy of chub mackerel and quinoa in reducing cognitive decline and retinal degeneration in the 5XFAD Alzheimer's mouse model

Alzheimer's disease (AD) is marked by cognitive decline and retinal degeneration. This study aimed to explore the potential of dietary chub mackerel ( Scomber colias ), rich in docosahexaenoic acid (DHA) and vitamin B12, and quinoa, as a source of vitamin B9, to prevent or delay these effects in a 5XFAD mouse model of AD. Thirty-two five-week-old male mice were divided into four groups: control, 10% chub mackerel, 5% quinoa, and 10% chub mackerel plus 5% quinoa, over 28 weeks. After 28 weeks, behavioural tests confirmed that none of the tested diets induced confounding effects related to anxiety-like behaviour or motor impairment. The diet combining chub mackerel and quinoa improved selected memory-associated outcomes and protected retinal integrity (p < 0.05), particularly within the neural layers. This diet also improved the brain n-3/n-6 PUFA ratio, primarily by reducing n-6 PUFA levels rather than by a significant increase in DHA. These benefits likely result from the complementary effects of key nutrients, including DHA and vitamins B9 and B12. The preservation of retinal thickness observed with the combined diet supports the use of retinal layer assessment as a potential non-invasive readout of AD-associated neurodegeneration. These findings indicate that combining chub mackerel and quinoa may help mitigate selected neurodegenerative and retinal alterations in the 5XFAD model, positioning them as promising components of a dietary strategy to support neuroprotection and retinal health during AD-related decline.