As preventative strategies in AD aim to modulate APP processing to lower the Aβ peptide and/or the other specific APP cleaved products with the use of secretase inhibitors, our data support further studies and understanding of the normal physiological functions of APP and its cleaved fragments, particularly with regards to the inflammatory innate immune responses and glial cell responses, to fully evaluate the efficacy and safety of such approaches in the clinic. This evidence concerns the gene APP and Alzheimer disease.