title: Tissue transglutaminase is not a biochemical marker for Alzheimer's disease.
abstract: Typical hallmarks of Alzheimer's disease (AD) are pathologic deposits in cortical and subcortical regions consisting of self-aggregated proteins such as amyloid-beta (Aβ) or tau. Tissue transglutaminase (tTG) catalyses calcium-dependent cross-linking between proteins (transamidation) resulting in protease-resistant isopeptide bonds. Because of this ability, tTG was suspected to participate in AD pathogenesis. Aβ and tau can be cross-linked by tTG in vitro. In AD neocortex, messenger RNA expression of tTG is increased. However, data on transamidation in AD specimens--activity of not only tTG but also other transglutaminases--are contradictory. The aim of our study was to investigate if tTG is involved in AD development and may be useful as biomarker for AD. We studied human brain samples for tTG concentration, tTG localization, and transamidation activity and cerebrospinal fluid (CSF) for tTG content by novel sensitive and highly specific methods. Neither tTG concentration nor transamidation was increased in AD brain homogenates. Immunohistologically, we found no colocalization of tTG in neocortex sections with tau or Aβ deposits but with blood vessels. Only in rare cases, tTG was detectable in CSF samples. This could be attributed to liberation from erythrocytes. Our data contradict the view that tTG is a potential biochemical marker for AD.
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics, University Hospital, Leipzig, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Wolf
authors.forename: Carsten
authors.initials: C
authors.lastname: Jäger
authors.forename: Ingolf
authors.initials: I
authors.lastname: Lachmann
authors.forename: Peter
authors.initials: P
authors.lastname: Schönknecht
authors.forename: Markus
authors.initials: M
authors.lastname: Morawski
authors.forename: Thomas
authors.initials: T
authors.lastname: Arendt
authors.forename: Thomas
authors.initials: T
authors.lastname: Mothes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000473:pathology*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology*; D005260:Female; D019204:GTP-Binding Proteins / Q000134:cerebrospinal fluid*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011180:Postmortem Changes; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000134:cerebrospinal fluid*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014841:von Willebrand Factor; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: Alzheimer's disease; Biomarker; Brain; Cerebrospinal fluid; Hemolysis; Tissue transglutaminase