The contact activation system and vascular factors as alternative targets for Alzheimer's disease therapy

• Main Authors: Pradeep K. Singh, Ana Badimon, Zu‐Lin Chen, Sidney Strickland, Erin H. Norris
• Format: Article
• Language: English
• Published: Wiley 2021-05-01
• Series: Research and Practice in Thrombosis and Haemostasis
• Subjects: Alzheimer's disease; beta‐amyloid; blood‐brain barrier; coagulation factors; contact system; dementia
• Online Access: https://doi.org/10.1002/rth2.12504

Abstract Alzheimer's disease (AD) is the most common neurodegenerative disease, affecting millions of people worldwide. Extracellular beta‐amyloid (Aβ) plaques and neurofibrillary tau tangles are classical hallmarks of AD pathology and thus are the prime targets for AD therapeutics. However, approaches to slow or stop AD progression and dementia by reducing Aβ production, neutralizing toxic Aβ aggregates, or inhibiting tau aggregation have been largely unsuccessful in clinical trials. The contribution of dysregulated vascular components and inflammation is evident in AD pathology. Vascular changes are detectable early in AD progression, so treatment of vascular defects along with anti‐Aβ/tau therapy could be a successful combination therapeutic strategy for this disease. Here, we explain how vascular dysfunction mechanistically contributes to thrombosis as well as inflammation and neurodegeneration in AD pathogenesis. This review provides evidence that addressing vascular dysfunction in people with AD could be a promising therapeutic strategy.