Soy flavonoids prevent cognitive deficits induced by intra-gastrointestinal administration of beta-amyloid

In Alzheimer's diseases, beta-amyloid may act as prion-like protein and migrate from the gastrointestinal tract towards the brain. Soy flavonoids have been identified as neuroprotective against cognitive loss in human. Diet with soy flavonoids may be used to slow down the progression of Alzheimer's diseases. We performed in-vitro tissue culture experiments using myenteric plexus longitudinal muscle layers isolated from the ileum and colon of ICR mice. Beta-amyloid can be taken up into myenteric neurons and induce neuron degeneration, which is protected by flavonoids compounds, including daidzein, genistein, glycitein and luteolin. We also administered oligomeric beta-amyloid (1–42) (total dose: 8 μg) into the gastrointestinal walls of ICR mice and conducted memory tests and gastrointestinal function assessments after 6 and 12 months. Mice treated with beta-amyloid exhibited minor learning deficits in a T-maze memory test at 6 months and significant memory impairment in a novel object recognition task at 12 months. These impairments were prevented by soy flavonoids. Tracking studies performed using fluorescently tagged beta-amyloid found that, beta-amyloid injected at the stomach can aggregate within the layer of myenteric neurons and migrate to the jejunum or via the vagus nerves to the brain after 1 month. Reductions in the gastrointestinal tissue weight and the spontaneous ileal contraction frequency were also observed at 6 and 12 months, respectively. Our findings indicate that beta-amyloid can migrate from the gastrointestinal tract to the brain to induce cognitive impairments. Furthermore, chronic soy flavonoids in drinking water have protective actions. [Display omitted] •Aβ can be up-taken by myenteric neurons in the GI tract.•Aβ induces myenteric neuron degeneration which is protected by soy flavonoids.•Aβ seeded at the GI tract can migrate to the vagus nerves and the brain in 1 month.•Aβ seeded at the GI tract can cause cognitive deficits 6 and 12 months after.•Chronic soy flavonoids treatment reverse the cognitive deficits.