Zhu and colleagues observed an exacerbated reduction in PIP2 in APOE4 carriers’ brains compared to APOE3. Decreased levels of PIP2 were associated with an increase in Synj1 [491], a PIP2-degrading enzyme [507] significantly upregulated in AD brains [508] and associated with reduced internalization and degradation of Aβ [509]. This evidence concerns the gene APOE and Alzheimer disease.