Related Experiment Video
Updated: May 17, 2026
Visualization of Amyloid β Deposits in the Human Brain with Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry
Published on: March 7, 2019
Tissue transglutaminase colocalizes with extracellular matrix proteins in cerebral amyloid angiopathy
Mieke de Jager1, Berend van der Wildt, Emma Schul
1Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands. am.dejager@vumc.nl
Insights
Tissue transglutaminase (tTG) plays a role in cerebral amyloid angiopathy (CAA), a hallmark of Alzheimer's disease. This study reveals tTG
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Cerebral amyloid angiopathy (CAA) is a critical feature of Alzheimer's disease (AD) and hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D).
- CAA involves amyloid-beta (Aβ) deposition and extracellular matrix (ECM) remodeling in cerebral vessels, contributing to AD and HCHWA-D progression.
- Tissue transglutaminase (tTG) is an enzyme that modifies the ECM through protein cross-linking.
Purpose of the Study:
- To investigate the distribution, cellular origin, and activity of tTG in cerebral amyloid angiopathy.
- To understand the role of tTG in the pathogenesis of CAA in control, AD, and HCHWA-D cases.
Main Methods:
- Immunohistochemistry to detect tTG and Aβ distribution and colocalization.
- Analysis of tTG and ECM protein presence in different vessel types and stages of CAA.
- Assessment of in situ tTG activity within the cerebral vessel wall.
Main Results:
- Increased tTG immunoreactivity and colocalization with Aβ in early CAA vessel walls.
- In later CAA stages, tTG and its cross-links formed halos around Aβ deposits, originating from astrocytes, fibroblasts, or endothelial cells.
- ECM proteins fibronectin and laminin were found within tTG-positive halos, and tTG activity was detected throughout the vessel wall in late-stage CAA.
Conclusions:
- tTG exhibits a changing distribution and cellular origin in CAA, suggesting a dynamic role in the disease.
- tTG activity may influence Aβ aggregation and ECM restructuring in cerebral amyloid angiopathy.
- These findings highlight tTG as a potential factor in CAA development and progression, impacting ECM integrity.
Abstract:
Cerebral amyloid angiopathy (CAA) is a key histopathological hallmark of Alzheimer's disease (AD) and hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D). CAA is characterized by amyloid-beta (Aβ) depositions and remodeling of the extracellular matrix (ECM) in brain vessels and plays an important role in the development and progression of both AD and HCHWA-D. Tissue transglutaminase (tTG) modulates the ECM by molecular cross-linking of ECM proteins. Here, we investigated the distribution pattern, cellular source, and activity of tTG in CAA in control, AD, and HCHWA-D cases. We observed increased tTG immunoreactivity and colocalization with Aβ in the vessel wall in early stage CAA, whereas in later CAA stages, tTG and its cross-links were present in halos enclosing the Aβ deposition. In CAA, tTG and its cross-links at the abluminal side of the vessel were demonstrated to be either of astrocytic origin in parenchymal vessels, of fibroblastic origin in leptomeningeal vessels, and of endothelial origin at the luminal side of the deposited Aβ. Furthermore, the ECM proteins fibronectin and laminin colocalized with the tTG-positive halos surrounding the deposited Aβ in CAA. However, we observed that in situ tTG activity was present throughout the vessel wall in late stage CAA. Together, our data suggest that tTG and its activity might play a differential role in the development and progression of CAA, possibly evolving from direct modulation of Aβ aggregation to cross-linking of ECM proteins resulting in ECM restructuring.
