Recently, using a mouse model of AD that express the mutant amyloid precursor protein (Mo/HuAPP695swe) and presenilin 1 (PS1-dE9) together with the active sterol regulatory element-binding transcription factor 2 (SREBF2), we have shown that the increase of cholesterol burden in the brain disrupts key mechanisms of cellular clearance resulting in an abnormal build-up of autophagosomes and defective Aβ disposal [18, 19]. This evidence concerns the gene SREBF2 and Alzheimer disease.