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

J Alzheimers Dis. 2020;73(4):1331-1342. doi: 10.3233/JAD-190997.

Abstract

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 β-lactolin improves memory retrieval and executive function and attenuates cognitive decline in the elderly. However, the effects of long-term consumption of β-lactolin on Alzheimer's disease (AD) pathologies have not been investigated. In the present study, we examined the effects of β-lactolin and whey digestion rich in β-lactolin on AD pathology in 5×FAD transgenic mice and PS19 tauopathy mice. Intake of β-lactolin and whey digestion rich in β-lactolin reduced the levels of inflammatory cytokines, suppressed the infiltration of activated microglia, decreased the levels of amyloid-β, 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×FAD transgenic mice. In addition, intake of β-lactolin and whey digestion rich in β-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 β-lactolin and whey digestion rich in β-lactolin suppresses inflammation and attenuates AD pathology and cognitive impairment.

Keywords: Alzheimer’s disease; amyloid-β; cognitive function; inflammation; memory; microglia; peptide; tauopathy; β-lactolin.

MeSH terms

  • Alzheimer Disease / pathology
  • Alzheimer Disease / prevention & control*
  • Alzheimer Disease / psychology
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Behavior, Animal / drug effects
  • Cognitive Dysfunction / pathology
  • Cognitive Dysfunction / prevention & control*
  • Cognitive Dysfunction / psychology
  • Cytokines / metabolism
  • Dopamine / metabolism
  • Macrophage Activation / drug effects
  • Memory / drug effects
  • Mice
  • Mice, Transgenic
  • Microglia / drug effects
  • Neurotransmitter Agents / metabolism
  • Oligopeptides / therapeutic use*
  • Psychomotor Performance / drug effects
  • Tauopathies / drug therapy
  • Whey Proteins / therapeutic use*

Substances

  • Amyloid beta-Peptides
  • Cytokines
  • Neurotransmitter Agents
  • Oligopeptides
  • Whey Proteins
  • beta-lactolin
  • Dopamine