PICALM and Alzheimer disease: With regard to aberrantly expressed mRNAs, we also verified four related mRNAs (Caspase 4, Picalm, Foxo3, and Pde8a), which we thought may be associated with the pathogenesis of Mn-induced neurotoxicity in accordance with the following reasons: Caspase 4 can act as an endoplasmic reticulum (ER) stress-specific caspase and may be associated with the pathology of AD in human [85].