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Transglutaminases and Transglutaminase-Catalyzed Cross-Links Colocalize with the Pathological Lesions in Alzheimer's Disease Brain
Micha M.M. Wilhelmus,
Sentini C.S. Grunberg,
John G.J.M. Bol,
Anne-Marie Van Dam,
Jeroen J.M. Hoozemans,
Annemieke J.M. Rozemuller,
Benjamin Drukarch,
Corresponding Author
Micha M.M. Wilhelmus
Department of Anatomy and Neurosciences, Institute for Clinical and Experimental Neurosciences (ICEN), and
Micha M.M. Wilhelmus, PhD, VU University Medical Center, Institute for Clinical and Experimental Neurosciences (ICEN), Department of Anatomy and Neurosciences, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands (E-mail: [email protected])Search for more papers by this authorSentini C.S. Grunberg
Department of Anatomy and Neurosciences, Institute for Clinical and Experimental Neurosciences (ICEN), and
Search for more papers by this authorJohn G.J.M. Bol
Department of Anatomy and Neurosciences, Institute for Clinical and Experimental Neurosciences (ICEN), and
Search for more papers by this authorAnne-Marie Van Dam
Department of Anatomy and Neurosciences, Institute for Clinical and Experimental Neurosciences (ICEN), and
Search for more papers by this authorJeroen J.M. Hoozemans
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Search for more papers by this authorAnnemieke J.M. Rozemuller
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Search for more papers by this authorBenjamin Drukarch
Department of Anatomy and Neurosciences, Institute for Clinical and Experimental Neurosciences (ICEN), and
Search for more papers by this authorMicha M.M. Wilhelmus,
Sentini C.S. Grunberg,
John G.J.M. Bol,
Anne-Marie Van Dam,
Jeroen J.M. Hoozemans,
Annemieke J.M. Rozemuller,
Benjamin Drukarch,
Corresponding Author
Micha M.M. Wilhelmus
Department of Anatomy and Neurosciences, Institute for Clinical and Experimental Neurosciences (ICEN), and
Micha M.M. Wilhelmus, PhD, VU University Medical Center, Institute for Clinical and Experimental Neurosciences (ICEN), Department of Anatomy and Neurosciences, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands (E-mail: [email protected])Search for more papers by this authorSentini C.S. Grunberg
Department of Anatomy and Neurosciences, Institute for Clinical and Experimental Neurosciences (ICEN), and
Search for more papers by this authorJohn G.J.M. Bol
Department of Anatomy and Neurosciences, Institute for Clinical and Experimental Neurosciences (ICEN), and
Search for more papers by this authorAnne-Marie Van Dam
Department of Anatomy and Neurosciences, Institute for Clinical and Experimental Neurosciences (ICEN), and
Search for more papers by this authorJeroen J.M. Hoozemans
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Search for more papers by this authorAnnemieke J.M. Rozemuller
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Search for more papers by this authorBenjamin Drukarch
Department of Anatomy and Neurosciences, Institute for Clinical and Experimental Neurosciences (ICEN), and
Search for more papers by this authorAbstract
Alzheimer's disease (AD) is characterized by pathological lesions, in particular senile plaques (SPs), cerebral amyloid angiopathy (CAA) and neurofibrillary tangles (NFTs), predominantly consisting of self-aggregated proteins amyloid beta (Aβ) and tau, respectively. Transglutaminases (TGs) are inducible enzymes, capable of modifying conformational and/or structural properties of proteins by inducing molecular covalent cross-links. Both Aβ and tau are substrates for TG cross-linking activity, which links TGs to the aggregation process of both proteins in AD brain. The aim of this study was to investigate the association of transglutaminase 1 (TG1), transglutaminase 2 (TG2) and TG-catalyzed cross-links with the pathological lesions of AD using immunohistochemistry. We observed immunoreactivity for TG1, TG2 and TG-catalyzed cross-links in NFTs. In addition, both TG2 and TG-catalyzed cross-links colocalized with Aβ in SPs. Furthermore, both TG2 and TG-catalyzed cross-links were associated with CAA. We conclude that these TGs demonstrate cross-linking activity in AD lesions, which suggests that both TG1 and TG2 are likely involved in the protein aggregation processes underlying the formation of SPs, CAA and/or NFTs in AD brain.
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