Ashton NJ, Nevado-Holgado AJ, Barber IS, Lynham S, Gupta V, Chatterjee P, Goozee K, Hone E, Pedrini S, Blennow K, Schöll M, Zetterberg H, Ellis KA, Bush AI, Rowe CC, Villemagne VL, Ames D, Masters CL, Aarsland D, Powell J, Lovestone S, Martins R, Hye A. A plasma protein classifier for predicting amyloid burden for preclinical Alzheimer's disease. Sci Adv. 2019 Feb;5(2):eaau7220. Epub 2019 Feb 6 PubMed.

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  1. The finding that decreased prothrombin was the highest-ranked feature in the Aβ+ cognitively unimpaired cohort is very intriguing. Thrombin derived from prothrombin is the last protease in the blood coagulation cascade. Aβ can activate Factor XII in the intrinsic coagulation pathway, which could ultimately lead to prothrombin depletion. This mechanism could partially explain the decrease in prothrombin observed in non-symptomatic Aβ-positive individuals.

    References:

    Zamolodchikov D, Chen ZL, Conti BA, Renné T, Strickland S. Activation of the factor XII-driven contact system in Alzheimer's disease patient and mouse model plasma. Proc Natl Acad Sci U S A. 2015 Mar 31;112(13):4068-73. Epub 2015 Mar 16 PubMed.

    Zamolodchikov D, Renné T, Strickland S. The Alzheimer's disease peptide β-amyloid promotes thrombin generation through activation of coagulation factor XII. J Thromb Haemost. 2016 May;14(5):995-1007. Epub 2016 Feb 29 PubMed.

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