The peripheral sink amyloid beta clearance pathway is defective in diabetes and Alzheimer’s disease. The release of amyloid beta (4 kd) monomers from neurons is associated with the amyloid beta clearance from the brain and determined by apolipoprotein E mediated transport of amyloid beta across the blood brain barrier to the periphery with rapid uptake by the liver. The role of microbiota has become of major interest to the treatment of Alzheimer’s disease and the gut bacterial composition needs to be determined that improve and accelerate the brain-liver amyloid beta clearance pathway with relevance to brain amyloidosis.
RELEVANT REFERENCES
1. Chandra, S., Sisodia, S.S. & Vassar, R.J. The gut microbiome in Alzheimer’s disease: what we know and what remains to be explored. Mol Neurodegeneration 18, 9 (2023).
2. Sharma, A and IJ Martins. The role of Microbiota in the pathogenesis of Alzheimer’s disease. Acta Scientific Nutritional Health. 7.7 (2023): 108-118.
3. Jin J, Xu Z, Zhang L, Zhang C, Zhao X, Mao Y, Zhang H, Liang X, Wu J, Yang Y, Zhang J. Gut-derived β-amyloid: Likely a centerpiece of the gut-brain axis contributing to Alzheimer's pathogenesis. Gut Microbes. 2023 Jan-Dec;15(1):2167172.
4. Appetite Regulation and the Peripheral Sink Amyloid beta Clearance Pathway in Diabetes and Alzheimer’s Disease. Top 10 Commentaries in Alzheimer’s Disease (e-book). 2019;2:1-11. www.avidscience.com
That is a very interesting question.
To begin with I'm not an expert in Abeta metabolism and clearance but I recently did some research on gut amyloids. Apparently, microbes inhabitating human gut are often capable of producing amyloids, mostly functional ones which they can use for biofilm formation adhesion etc. (There was an excelent paper on that topic published recently (https://www.nature.com/articles/s41467-024-48309-x).
So it is quite likely that our organisms needs to have some mechanisms of removing these amyloids. Due to structural similarities of functional amyloids to their pathological counterparts it seems quite possible that similar mechanisms can be used to clear them out. In such a case the clearence pathway might simply be overloaded with bacterial amyloids and can not efficiently remove AB.
What do you think about it?
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