This paper is devoted to develop a new mathematical model for Alzheimer disease based on a system of fractional-order partial differential equations. The system of Alzheimer disease includes neurons, astrocytes, microglias and peripheral macrophages, as well as amyloid β aggregation and hyperphosphorylated tau proteins. We consider the Caputo fractional derivative definition to analyze the formulated system by simulating the effect of drugs that either failed or currently in clinical trials. To simulate the model, we use tight frame (framelet) systems generated using the unitaryand oblique extension principle. According to the simulation results, and based on using such new direction of fractional modeling, the progression of Alzheimer disease and its consequences will be slowing down. Which may give clinical insights on intervention measures against the disease and its effective therapies. © 2021 The Author(s)