Daily supplementation with egg yolk lipids from two eggs alleviated cognitive impairment in 5 × FAD mice by restoring neuronal and synaptic function and regulating gut microbiota.

Eggs are recommended by dietary guidelines as an effective vehicle for DHA intake, yet direct evidence on the health effects and optimal dosage of egg yolk lipids against Alzheimer's disease (AD) remains limited. This study evaluated DHA-enriched egg yolk lipids in 5 × FAD mice at doses of 1 and 2 g kg-1 day-1 for eight weeks, corresponding to human consumption of 1 or 2 eggs daily. The high-dose intervention (2 g kg-1) ameliorated cognitive deficits and neuronal damage by upregulating BDNF and NGF, improving synaptic plasticity (PSD95, SYN, Drebrin), increasing dendritic spine density, restoring cholinergic and glutamatergic neurons, and suppressing microglial activation-induced neuroinflammation (IL-6, IL-1β, IFN-γ). Metabolomic and gut microbiota analysis revealed increased levels of neuroprotective metabolites (PC (20 : 2/22 : 6), neuroprotectin D1) and enhanced abundance of AD-beneficial genera including Muribaculaceae and Lachnospiraceae. This study provides direct experimental evidence supporting DHA-enriched egg yolk lipids as a dietary intervention strategy for AD, with an effective dosage of 2 g kg-1.