title: Catalytically active tissue transglutaminase colocalises with Aβ pathology in Alzheimer's disease mouse models.
abstract: Alzheimer's disease (AD) is characterised by amyloid-beta (Aβ) protein deposition in the brain. Posttranslational modifications in Aβ play an important role in Aβ deposition. Tissue transglutaminase (tTG) is an enzyme involved in posttranslational cross-linking of proteins. tTG levels and activity are increased in AD brains, and tTG is associated with Aβ deposits and lesion-associated astrocytes in AD cases. Furthermore, Aβ is a substrate of tTG-catalysed cross-linking. To study the role of tTG in Aβ pathology, we compared tTG distribution and activity in both the APPSWE/PS1ΔE9 and APP23 mice models with human AD. Using immunohistochemistry, we found association of both tTG and in situ active tTG with Aβ plaques and vascular Aβ, in early and late stages of Aβ deposition. In addition, tTG staining colocalised with Aβ-associated reactive astrocytes. Thus, alike human AD cases, tTG was associated with Aβ depositions in these AD models. Although, distribution pattern and spatial overlay of both tTG and its activity with Aβ pathology was substantially different from human AD cases, our findings provide evidence for an early role of tTG in Aβ pathology. Yet, species differences should be taken into account when using these models to study the role of tTG in Aβ pathology.
authors.affiliation: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU medical center, Amsterdam, The Netherlands.
authors.forename: Micha M M
authors.initials: MM
authors.lastname: Wilhelmus
authors.affiliation: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU medical center, Amsterdam, The Netherlands.
authors.forename: Mieke
authors.initials: M
authors.lastname: de Jager
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, the Netherlands.
authors.forename: August B
authors.initials: AB
authors.lastname: Smit
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, the Netherlands.
authors.forename: Rolinka J
authors.initials: RJ
authors.lastname: van der Loo
authors.affiliation: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU medical center, Amsterdam, The Netherlands.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Drukarch
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D020134:Catalytic Domain; D004195:Disease Models, Animal; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D058225:Plaque, Amyloid / Q000378:metabolism; D011503:Transglutaminases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D011503:Transglutaminases
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