β-Lactolin, a Whey-Derived Lacto-Tetrapeptide, Prevents Alzheimer's Disease Pathologies and Cognitive Decline

The prevention of age-related memory decline and dementia has been becoming a high priority because of the rapid growth in aging populations. Accumulating epidemiological and clinical studies indicate that intake of fermented dairy products rich in beta-lactolin improves memory retrieval and executive function and attenuates cognitive decline in the elderly. However, the effects of long-term consumption of beta-lactolin on Alzheimer's disease (AD) pathologies have not been investigated. In the present study, we examined the effects of beta-lactolin and whey digestion rich in beta-lactolin on AD pathology in 5 x FAD transgenic mice and PS19 tauopathy mice. Intake of beta-lactolin and whey digestion rich in beta-lactolin reduced the levels of inflammatory cytokines, suppressed the infiltration of activated microglia, decreased the levels of amyloid-beta, ameliorated impaired long-term object memory, and attenuated decreased synaptophysin, dopamine, brain-derived neurotrophic factor, and insulin-like growth factor 1 levels in the cortex in 5 x FAD transgenic mice. In addition, intake of beta-lactolin and whey digestion rich in beta-lactolin improved behavioral abnormality and reduced the ratio of phosphorylated tau to total tau in the cortex in PS19 tauopathy mice. These findings indicate that consumption with beta-lactolin and whey digestion rich in beta-lactolin suppresses inflammation and attenuates AD pathology and cognitive impairment.