Histopathologically, numerous senile plaques and neurofibrillary tangles were remarkably observed in the brain with Alzheimer's disease. At the same time, so much simple atrophy of nerve cells was evident under light microscopy. Electron microscopical observations of serial sections revealed that small blood vessels, including capillaries, had a deep relationship to the amyloid fibrils which formed the senile plaques and they had fallen into degenerative states. The vascular feet of the astroglial cells surrounding small blood vessels showed degenerative features, and many nerve cells in this area either showed various degrees of degeneration or apparently were destroyed. The atrophy of the brain with Alzheimer's disease is considered to be caused by the amyloid angiopathy of small blood vessels and the degeneration of capillaries and vascular feet. These findings strongly suggest that the major causal mechanism of Alzheimer's disease is an alteration of the blood–brain barrier. Morphology is an expression of both the structure and the function of organs in the living body. Based on this viewpoint, this review article emphasizes that the morphological changes to small blood vessels in the brain with Alzheimer's disease convey crucial information and clues for solving the underlying mechanism that causes the disease.