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Alzheimer disease

Primate study deals a fresh blow to the peripheral sink hypothesis

Nature Reviews Neurology volume 10, page 4 (2014)Cite this article

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The peripheral sink hypothesis—the idea that levels of soluble amyloid-β (Aβ) in the brain and the periphery are in equilibrium, such that peripheral depletion of Aβ should lead to removal of Aβ from the brain—has prompted preclinical trials of Aβ-degrading agents. The results to date, however, have been disappointing: one study reported in early 2013 showed that brain levels of Aβ remained unchanged in a mouse model of AD after treatment with the Aβ-degrading protease neprilysin. A new study has extended these findings to rats and monkeys. After 1 month of treatment with neprilysin in these animals, peripheral Aβ levels were substantially decreased, but brain and cerebrospinal fluid levels were unaffected. The authors suggest that these findings invalidate the peripheral sink hypothesis.

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References

  1. Henderson, S. J. et al. Sustained peripheral depletion of amyloid-β with a novel form of neprilysin does not affect central levels of amyloid-β. Brain 10.1093/brain/awt308

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Walker, J. R. et al. Enhanced proteolytic clearance of plasma Aβ by peripherally administered neprilysin does not result in reduced levels of brain Aβ in mice. J. Neurosci. 33, 2457–2464 (2013)

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Primate study deals a fresh blow to the peripheral sink hypothesis. Nat Rev Neurol 10, 4 (2014). https://doi.org/10.1038/nrneurol.2013.266

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