In our understanding, breaking the physiological internalization of the Aβ42-LRP1 complexes with Aβ42 anchored in amyloid fibrils causes a gradual dysfunction of unmyelinated neuronal membranes, resulting in classic “tauopathy.” This theory anticipates two substantial considerations: (1) other “tauopathies” are probably caused by either extracellular or intracellular membrane dysfunction, and (2) simply targeting Aβ42 fibrils will not lead to an effective anti-AD therapy. The gene discussed is LRP1; the disease is Alzheimer disease.