Blood will out: vascular contributions to Alzheimer’s disease
Sidney Strickland
Sidney Strickland
Published February 1, 2018
Citation Information: J Clin Invest. 2018;128(2):556-563. https://doi.org/10.1172/JCI97509.
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Review

Blood will out: vascular contributions to Alzheimer’s disease

Abstract

The fundamental pathology in Alzheimer’s disease (AD) is neuronal dysfunction leading to cognitive impairment. The amyloid-β peptide (Aβ), derived from amyloid precursor protein, is one driver of AD, but how it leads to neuronal dysfunction is not established. In this Review, I discuss the complexity of AD and possible cause-and-effect relationships between Aβ and the vascular and hemostatic systems. AD can be considered a multifactorial syndrome with various contributing pathological mechanisms. Therefore, as is routinely done with cancer, it will be important to classify patients with respect to their disease signature so that specific pathologies, including vascular pathways, can be therapeutically targeted.

Authors

Sidney Strickland

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Figure 3

The contact activation system.

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The contact activation system. Aβ-mediated dysregulation or overactivati...
Aβ-mediated dysregulation or overactivation of the contact system could contribute to the coagulopathy and inflammation observed in AD. Aβ can trigger activation of factor XII (FXII) into FXIIa. FXIIa’s activation of FXI initiates the intrinsic coagulation system and fibrin formation, whereas its activation of plasma prekallikrein leads to inflammation. PPK, plasma prekallikrein; PK, plasma kallikrein; HK, high molecular weight kininogen; HKc, cleaved HK. a = activated form.