title: Fibrin deposited in the Alzheimer's disease brain promotes neuronal degeneration.
abstract: Alzheimer's disease (AD) is the most common form of dementia and has no effective treatment. Besides the well-known pathologic characteristics, this disease also has a vascular component, and substantial evidence shows increased thrombosis as well as a critical role for fibrin(ogen) in AD. This molecule has been implicated in neuroinflammation, neurovascular damage, blood-brain barrier permeability, vascular amyloid deposition, and memory deficits that are observed in AD. Here, we present evidence demonstrating that fibrin deposition increases in the AD brain and correlates with the degree of pathology. Moreover, we show that fibrin(ogen) is present in areas of dystrophic neurites and that a modest decrease in fibrinogen levels improves neuronal health and ameliorates amyloid pathology in the subiculum of AD mice. Our results further characterize the important role of fibrin(ogen) in this disease and support the design of therapeutic strategies aimed at blocking the interaction between fibrinogen and amyloid-β (Aβ) and/or normalizing the increased thrombosis present in AD.
authors.affiliation: Patricia and John Rosenwald, Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Cortes-Canteli
authors.affiliation: Patricia and John Rosenwald, Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY, USA.
authors.forename: Larissa
authors.initials: L
authors.lastname: Mattei
authors.affiliation: Patricia and John Rosenwald, Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY, USA.
authors.forename: Allison T
authors.initials: AT
authors.lastname: Richards
authors.affiliation: Patricia and John Rosenwald, Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY, USA.
authors.forename: Erin H
authors.initials: EH
authors.lastname: Norris
authors.affiliation: Patricia and John Rosenwald, Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY, USA. Electronic address: strickland@rockefeller.edu.
authors.forename: Sidney
authors.initials: S
authors.lastname: Strickland
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D005337:Fibrin / Q000378:metabolism* / Q000502:physiology*; D005340:Fibrinogen / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000235:genetics; D020767:Intracranial Thrombosis / Q000209:etiology / Q000628:therapy; D008569:Memory Disorders / Q000209:etiology / Q000235:genetics; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016501:Neurites / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*
chemical_list: D016229:Amyloid beta-Peptides; D005337:Fibrin; D005340:Fibrinogen
keywords: Alzheimer's disease; Coagulation; Fibrinogen; Neurodegeneration