Murine models of brain aging and age-related neurodegenerative diseases

In the past, structural changes in the brain with aging have been studied using a variety of animal models, with rats and nonhuman primates being the most popular. With the rapid evolution of mouse genetics, murine models have gained increased attention in the neurobiology of aging. The genetic contribution of age-related traits as well as specific mechanistic hypotheses underlying brain aging and age-related neurodegenerative diseases can now be assessed by using genetically-selected and genetically-manipulated mice. Against this background of increased demand for aging research in mouse models, relatively few studies have examined structural alterations with aging in the normal mouse brain, and the data available are almost exclusively restricted to the C57BL/6 strain. Moreover, many older studies have used quantitative techniques which today can be questioned regarding their accuracy. Here we review the state of knowledge about structural changes with aging in outbred, inbred, genetically-selected, and genetically-engineered murine models. Moreover, we suggest several new opportunities that are emerging to study brain aging and age-related neurodegenerative diseases using genetically-defined mouse models. By reviewing the literature, it has become clear to us that in light of the rapid progress in genetically-engineered and selected mouse models for brain aging and age-related neurodegenerative diseases, there is a great and urgent need to study and define morphological changes in the aging brain of normal inbred mice and to analyze the structural changes in genetically-engineered mice more carefully and completely than accomplished to date. Such investigations will broaden knowledge in the neurobiology of aging, particularly regarding the genetics of aging, and possibly identify the most useful murine models.