H-GLU(H-LYS-OH)-OH

H-Glu(H-Lys-OH)-OH for Colocalization of TG-Catalyzed Crosslinks with AD Brain Pathology

Wilhelmus, Micha MM, et al. Brain Pathology, 2009, 19(4), 612-622.

Transglutaminase (TG) is an inducible enzyme that can change the conformation and/or structural properties of proteins by inducing covalent crosslinking of molecules. Here, immunohistochemistry was used to investigate the relationship between transglutaminase 1 (TG1), transglutaminase 2 (TG2), and TG-catalyzed crosslinks and AD pathology. This work involved the use of H-Glu(H-Lys-OH)-OH to verify the colocalization of TG-catalyzed crosslinks with AD brain pathology.
Colocalization of TG-catalyzed cross-links with the pathological lesions in AD brains
· Overall, the TG-catalyzed cross-link staining pattern in the neocortex of Alzheimer's disease (AD) was comparable to that in control brains. Approximately 96% of the diffuse senile plaques (SPs) (Figure 4A,B) and all classic SPs (Figure 4C,D) exhibited TG-catalyzed cross-link staining. Additionally, TG-catalyzed cross-links were noted in reactive astrocytes associated with SPs (Figure 4D).
· Similar to the TG2 staining in vessels impacted by CAA, an abluminal staining of the TG-catalyzed cross-link antibody indicated increased cross-linking in perivascular cells (Figure 4G-I). Moreover, TG-catalyzed cross-link staining was found to colocalize with hyperphosphorylated tau protein in neurofibrillary tangles (NFTs) (Figure 4J-L) and in tau-positive neuritic changes associated with SPs, though it was absent in pretangles.
· Approximately 95% of the NFTs exhibited TG-catalyzed cross-link staining. The specificity of the anti-TG-catalyzed cross-link reactivity in human brains was validated by significantly reduced staining of the anti-TG-catalyzed cross-link antibody (Figure 4M) following preadsorption with H-Glu(H-Lys-OH)-OH (Figure 4N).