In further studies, the researchers found that TIA1 mutations occurred frequently in ALS patients. The scientists also found that people carrying the mutation had the disease. When the investigators analyzed brain tissue from deceased ALS patients with the mutations, the scientists detected a buildup of TIA1-containing organelles called stress granules in the neurons. Such granules form when the cell experiences such stresses as heat, chemical exposure and aging. To survive, the cell sequesters in the granules' genetic material that codes for cell proteins not necessary for survival-critical processes.
The granules also contained a protein called TDP-43, another building block of stress granules, whose abnormality has been implicated in causing ALS. In test tube studies and experiments with cells, the researchers found that the TIA1 mutation causes the protein to become more "sticky," delaying the normal disassembly of stress granules, trapping TDP-43.