Beta-amyloid in the Gastrointestinal Tract May Cause Cognitive Deficits: Protective Action of Soy Flavonoids
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摘要Introduction: Beta-amyloid (Aβ) can be found in the gastrointestinal (GI) tract of Alzheimer’s disease (AD) patients. [1] This is important, since an emerging hypothesis suggests that protein aggregates seen in neurological diseases such as Aβ and α-synuclein in Alzheimer’s disease and Parkinson’s disease respectively, could transport from periphery to the brain like a prion disease. [2] Evidence for α-synuclein to spread from the GI tract via the vagus nerves to the brain through protein-transport mechanisms had been published recently. [3]

Objectives: A similar mechanism may contribute to the appearance of Aβ in the brains of AD patients and to contribute to cognitive loss. In previous in-vitro studies, we found that soy bean flavonoids could protect enteric nerves from Aβ toxicity. The use of soy bean flavonoids may be a safer option for hormone replacement therapy, which is also an economical option for long-term treatment and prevention of AD. We are interested in whether peripheral seeded Aβ along the gastrointestinal tract will lead to cognitive loss and whether daily oral intake of soy bean flavonoids will prevent this in a 12 month long study.

Methods: In the present studies, we performed surgery to inject oligomeric Aβ (total dose, 8 μg/mouse) along the serosal lining of GI tract and then performed a battery of memory tests 6-12 months later on 2 month old female ICR mouse. In separate surgical groups, soy flavonoids, (1) daidzein, (2) genistein, (3) glycitein, and (4) a
mixed formula (DAI/GEN/GLY=4:6:1) were given daily in drinking water (Approx. dose, 400ug/day/mouse). At termination, electrical frequency stimulation of GI tissues was performed to analysis GI neuronal functions.

Results: We found that GI-seeded Aβ induced cognitive deficits in the novel object recognition test, which was prevented by daily oral intake of soy flavonoids, in all four treatment groups. (p<0.01) However, Aβ did not disrupt learning and memory in the Morris water maze, passive avoidance task, or hunger-driven T-maze task. No significant difference was observed in GI functional assay. (p>0.05)

Conclusion: We conclude that GI-seeded Aβ may induce cognitive deficits in spontaneous memory tasks, but not in tasks confounded by internal stress factors, like pain. The type of memory being affected had yet to be determined. We are currently investigating the impact of Aβ treatment on the brain and GI tract using molecular biology.

1. Joachim CL, et al. (1989) Amyloid beta-protein deposition in tissues other than brain in Alzheimer’s disease, Nature, 341(6239):226-30.
2. Natale G., et al. (2011) Parallel manifestations of neuropathologies in the enteric and central nervous systems, Neurogastroenterol. Motil., 23(12):1056-65.
3. Holmgvist S., et al. (2014) Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats, Acta Neuropathol., 128(6):805-20.
著者Julia Y.H. Liu, Ge Lin and John A. Rudd
會議名稱32nd International Conference of Alzheimer's Disease International
會議開始日26.04.2017
會議完結日29.04.2017
會議地點Kyoto
會議國家/地區日本
出版年份2017
月份4
語言美式英語

上次更新時間 2018-22-01 於 09:19