Three-Dimensional Imaging of Fibrinogen and Neurovascular Alterations in Alzheimer's Disease.

Abstract

Cerebrovascular dysfunction is a hallmark of Alzheimer's disease (AD) that is linked to cognitive decline. However, blood-brain barrier (BBB) disruption in AD is focal and requires sensitive methods to detect extravasated blood proteins and vasculature in large brain volumes. Fibrinogen, a blood coagulation factor, is deposited in AD brains at sites of BBB disruption and cerebrovascular damage. This chapter presents the methodology of fibrinogen immunolabeling-enabled three-dimensional (3D) imaging of solvent-cleared organs (iDISCO) which, when combined with immunolabeling of amyloid β (Aβ) and vasculature, enables sensitive detection of focal BBB vascular abnormalities, and reveals the spatial distribution of Aβ plaques and fibrin deposits, in large tissue volumes from cleared human brains. Overall, fibrinogen iDISCO enables the investigation of neurovascular and neuroimmune mechanisms driving neurodegeneration in disease.

• Authors: Mario Merlini, Elif G Sozmen, Keshav S Subramanian, Alissa L Nana, William W Seeley, Katerina Akassoglou
• Journal: Methods in molecular biology (Clifton, N.J.) (Methods Mol Biol) Vol. 2561 Pg. 87-101 ( 2023) ISSN: 1940-6029 [Electronic] United States
• PMID: 36399266 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: © 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Amyloid beta-Peptides
• Fibrinogen

Topics

• Humans
• Alzheimer Disease (metabolism)
• Amyloid beta-Peptides (metabolism)
• Fibrinogen (metabolism)
• Imaging, Three-Dimensional
• Plaque, Amyloid