Key Information
Transthyretin (TTR) is a tetrameric protein that transports hormones in plasma and the brain, primarily expressed in hepatocytes. TTR is a positive indicator of nutritional status and negatively correlated with inflammation. TTR is a neuroprotective factor and an inhibitor of oxidative stress. The core pathology of TTR amyloidosis lies in the loss of tetrameric kinetic stability. The rate-limiting step is the dissociation of the tetramer into monomers, which subsequently misfold and self-assemble into various aggregate structures, including amyloid fibrils. These insoluble fibrils deposit in the extracellular matrix, forming amyloid plaques. These deposits pathologically infiltrate tissues such as the heart and peripheral nerves, causing mechanical compression, disrupting normal tissue structure, and leading to transthyretin amyloid cardiomyopathy (ATTR-CM).