Patterson BW, Elbert DL, Mawuenyega KG, Kasten T, Ovod V, Ma S, Xiong C, Chott R, Yarasheski K, Sigurdson W, Zhang L, Goate A, Benzinger T, Morris JC, Holtzman D, Bateman RJ. Age and amyloid effects on human central nervous system amyloid-beta kinetics. Ann Neurol. 2015 Sep;78(3):439-53. Epub 2015 Jul 20 PubMed.
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University of Melbourne
These results of the Aβ CSF kinetics on 112 subjects are a major advance in quantification of the deposition and accumulation of Aβ in the AD brain. The increase in half-life from 3.8 hours to 9.4 hours over a 50-year time span is exactly the information we require in devising therapeutic interventions that can change the rate of Aβ accumulation. We suspect that the biochemical pool of Aβ that is being measured in the CSF is a reflection of the more soluble/diffusible pool in the interstitial fluid space, whereas the Aβ-PET signals reflect the more insoluble/less diffusible pools. As we learn more of the turnover of these different Aβ pools, we will eventually be able to pull the jigsaw puzzle of Aβ kinetics together into one coherent dynamic equilibrium. The key figure in Patterson’s paper may lie in the discussion, where they estimate that the rate of deposition of Aβ into the insoluble plaque pool is 31 ng/h or 273 μg/year. This is consistent with our current estimates based on Aβ-PET and post-mortem studies (Roberts et al., manuscript in preparation). Abrogating this rate of deposition using Aβ-targeted therapeutics is not an insurmountable challenge.
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