Recent studies have revealed the presence of tau protein-immunoreactive accumulations and β amyloid protein (Aβ) deposits in the cerebral cortex of the aged mouse lemur, Microcebus murinus. To examine the age-related evolution of these changes and compare their regional distribution to that reported for humans and nonhuman primates with Alzheimer’s disease lesions, we performed a quantitative analysis of a large series of mouse lemurs aged from 1 to 13 years. The prevalence and density of tau protein-immunoreactive accumulations in the neocortex of this prosimian increased steadily with age. Neocortical areas were frequently affected even in young mouse lemurs, whereas the subiculum and entorhinal cortex were only involved occasionally in animals older than 8 years. As in anthropoid primates, diffuse Aβ deposits were often observed in the cerebral cortex and amygdala of old mouse lemurs. Although all animals with diffuse Aβ deposits had tau protein-immunoreactive accumulations in the neocortex, no correlation was found between the densities of these lesions in each area and among the areas studied. The age-dependent progression of tau protein-immunoreactive accumulations indicates that this prosimian may represent a valuable model for the study of the biochemical mechanisms of brain aging, while the relative sparing of hippocampus in mouse lemurs contrasts sharply with previous reports on neurofibrillary tangle formation in humans, and suggests that this animal may also be useful to investigate the biological characteristics of neuroprotection in this area. Furthermore, the present data indicate that Aβ deposition in mouse lemurs is not age dependent, but occurs in a few vulnerable old animals.