Affiliation:
1. Patricia and John Rosenwald Laboratory of Neurobiology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
Abstract
Alzheimer’s disease (AD) is the most common neurodegenerative disease, affecting millions of people worldwide. The classical hallmarks of AD include extracellular beta-amyloid (Aβ) plaques and neurofibrillary tau tangles, although they are often accompanied by various vascular defects. These changes include damage to the vasculature, a decrease in cerebral blood flow, and accumulation of Aβ along vessels, among others. Vascular dysfunction begins early in disease pathogenesis and may contribute to disease progression and cognitive dysfunction. In addition, patients with AD exhibit alterations in the plasma contact system and the fibrinolytic system, two pathways in the blood that regulate clotting and inflammation. Here, we explain the clinical manifestations of vascular deficits in AD. Further, we describe how changes in plasma contact activation and the fibrinolytic system may contribute to vascular dysfunction, inflammation, coagulation, and cognitive impairment in AD. Given this evidence, we propose novel therapies that may, alone or in combination, ameliorate AD progression in patients.
Funder
National Institutes of Health
Alzheimer’s Drug Discovery Foundation
Samuel I. Newhouse Foundation
May and Samuel Rudin Family Foundation
Mr. John A. Herrmann, Jr., and the Kellen Women’s Entrepreneurship Fund
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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