title: Transglutaminases and transglutaminase-catalyzed cross-links colocalize with the pathological lesions in Alzheimer's disease brain.
abstract: 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 (Abeta) 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 Abeta 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 Abeta 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.
authors.affiliation: Department of Anatomy and Neurosciences, Institute for Clinical and Experimental Neurosciences, VU University Medical Center, Amsterdam, The Netherlands. m.wilhelmus@vumc.nl
authors.forename: Micha M M
authors.initials: MM
authors.lastname: Wilhelmus
authors.forename: Sentini C S
authors.initials: SC
authors.lastname: Grunberg
authors.forename: John G J M
authors.initials: JG
authors.lastname: Bol
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: van Dam
authors.forename: Jeroen J M
authors.initials: JJ
authors.lastname: Hoozemans
authors.forename: Annemieke J M
authors.initials: AJ
authors.lastname: Rozemuller
authors.forename: Benjamin
authors.initials: B
authors.lastname: Drukarch
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016657:Cerebral Amyloid Angiopathy / Q000150:complications / Q000378:metabolism / Q000473:pathology; D003432:Cross-Linking Reagents / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000378:metabolism* / Q000473:pathology*; D016874:Neurofibrillary Tangles / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D011503:Transglutaminases / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D003432:Cross-Linking Reagents; D016875:tau Proteins; D011503:Transglutaminases