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: Marta Cortes-Canteli, Larissa Mattei, Allison T Richards, Erin H Norris, Sidney Strickland
• Journal: Neurobiology of aging (Neurobiol Aging) Vol. 36 Issue 2 Pg. 608-17 (Feb 2015) ISSN: 1558-1497 [Electronic] United States
• PMID: 25475538 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Fibrin
• Fibrinogen

Topics

• Alzheimer Disease (genetics, metabolism, pathology)
• Amyloid beta-Peptides (metabolism)
• Animals
• Blood-Brain Barrier (metabolism)
• Brain (metabolism, pathology)
• Fibrin (metabolism, physiology)
• Fibrinogen (metabolism, physiology)
• Humans
• Inflammation (genetics)
• Intracranial Thrombosis (etiology, therapy)
• Memory Disorders (etiology, genetics)
• Mice, Transgenic
• Molecular Targeted Therapy
• Nerve Degeneration (genetics, metabolism, pathology)
• Neurites (metabolism, pathology)
• Neurons (metabolism, pathology)