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Posttranslational modifications in A\u03b2 play an important role in A\u03b2 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 A\u03b2 deposits and lesion-associated astrocytes in AD cases. Furthermore, A\u03b2 is a substrate of tTG-catalysed cross-linking. To study the role of tTG in A\u03b2 pathology, we compared tTG distribution and activity in both the APP<jats:sub>SWE<\/jats:sub>\/PS1<jats:sub>\u0394E9<\/jats:sub> and APP23 mice models with human AD. Using immunohistochemistry, we found association of both tTG and <jats:italic>in situ<\/jats:italic> active tTG with A\u03b2 plaques and vascular A\u03b2, in early and late stages of A\u03b2 deposition. In addition, tTG staining colocalised with A\u03b2-associated reactive astrocytes. Thus, alike human AD cases, tTG was associated with A\u03b2 depositions in these AD models. Although, distribution pattern and spatial overlay of both tTG and its activity with A\u03b2 pathology was substantially different from human AD cases, our findings provide evidence for an early role of tTG in A\u03b2 pathology. Yet, species differences should be taken into account when using these models to study the role of tTG in A\u03b2 pathology.<\/jats:p>","DOI":"10.1038\/srep20569","type":"journal-article","created":{"date-parts":[[2016,2,3]],"date-time":"2016-02-03T11:22:46Z","timestamp":1454498566000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Catalytically active tissue transglutaminase colocalises with A\u03b2 pathology in Alzheimer\u2019s disease mouse models"],"prefix":"10.1038","volume":"6","author":[{"given":"Micha M. 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