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 1

Multiple pathogenic pathways contribute to and provide therapeutic targets for AD.

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Multiple pathogenic pathways contribute to and provide therapeutic targe...
While neuronal dysfunction is the defining pathology underlying cognitive decline in AD, this disease is likely the product of multiple pathogenic mechanisms and might benefit from combination therapy (128–130). Increasing evidence implicates vascular dysfunction in AD pathogenesis. Aβ plaques and tau tangles drive neuronal dysfunction and neuroinflammation through mechanisms that are not fully established. Aβ is also implicated in vascular pathology, having been shown to interact with fibrin(ogen) and the contact system. The prevalence of vascular dysfunction in patients exhibiting cognitive decline suggests that combining existing treatment strategies targeting neuronal dysfunction (e.g., cholinesterase inhibitors) and vascular dysfunction (e.g., antiinflammatory, antihypertensive, or anticoagulant medications) may advance AD treatment efficacy.