Pathophysiological concentrations of Aβ inhibit PI4K (generates PI(4)P) activity, both in vitro and in vivo.PI4K inhibition reduces brain pathology in Drosophila models of AD.VAPB, a causal gene for ALS, exerts deleterious effects in the brain by altering PI(4)P levels and distribution. Reduced in AD cortex. Here, VAPB is linked to Alzheimer disease.