TGM2 and Alzheimer disease: Interestingly, isodipeptide bonds reportedly co-localize with paired helical filaments (PHFs) in the parietal and frontal cortex, lacking microscopically detectable NFT in stage II AD, suggesting that the TG2 catalyzed crosslinking of tau is an early event in the formation of PHF, prior to the appearance of NFT in AD [139].