Intracerebroventricular‐injected fibroblast growth factor (FGF)‐2 causes cerebrospinal fluid (CSF) stagnation and a normal‐pressure hydrocephalus (NPH)‐like syndrome in rats. NPH may be part of a pathophysiologic continuum culminating in Alzheimer disease (AD), at least in the context of amyloid‐β (Aβ) retention and plaque formation. We have examined transgenic mice with variable degrees of FGF‐2 and Aβ generation within the CNS and have active breeding pairs of TgFGF2xTgAPP (APP = amyloid precursor protein) to provide TgFGF2, TgAPP, and TgFGF2xTgAPP offspring. A coronal section was made through fixed cerebral hemispheres, with the anterior commissure and posterior limit of the optic chiasm used as sectioning landmarks. Serial 10 μm coronal sections were cut from the caudal portion of the hemispheres using a freezing microtome. A striking finding was the presence of flattened and denuded ependyma in the APPxFGF2 overexpressor mice, indicative of early hydrocephalus, and increased Aβ 1–42 neuronal expression in these mice. Similar changes were not observed in APP control mice. This strongly suggests that growth factor overexpression will accelerate the development of Aβ production and AD pathology.