Microcebus murinus: a useful primate model for human cerebral aging and Alzheimer's disease?

Abstract

Age-associated dementia, in particular Alzheimer's disease (AD), will be a major concern of the 21st century. Research into normal brain aging and AD will therefore become increasingly important. As for other areas of medicine, the availability of good animal models will be a limiting factor for progress. Given the complexity of the human brain, the identification of appropriate primate models will be essential to further knowledge of the disease. In this review, we describe the features of brain aging and age-associated neurodegeneration in a small lemurian primate, the Microcebus murinus, also referred to as the mouse lemur. The mouse lemur has a relatively short life expectancy, and animals over 5 years of age are considered to be elderly. Among elderly mouse lemurs, the majority show normal brain aging, whereas approximately 20% develop neurodegeneration. This Microcebus age-associated neurodegeneration is characterized by a massive brain atrophy, abundant amyloid plaques, a cytoskeletal Tau pathology and a loss of cholinergic neurons. While elderly mouse lemurs with normal brain aging maintain memory function and social interaction, animals with age-associated neurodegeneration lose their cognitive and social capacities and demonstrate certain similarities with age-associated human AD. We conclude that M. murinus is an interesting primate model for the study of normal brain aging and the biochemical dysfunctions occurring in age-associated neurodegeneration. Mouse lemurs might also become an increasingly important model for the development of novel treatments in this domain.

Distribution of lithostathine in the mouse lemur brain with aging and Alzheimer's-like pathology

“…With age, loss of cholinergic neurones was evidenced in the basal telencephalon in some animals (Mestre and Bons, 1993). In addition, lemurian primate presents similar aging characteristics as those observed in humans, such as modifications of the biological rhythms (Perret and Aujard, 2006), cognitive alterations (Picq, 1995;Picq, 2007;Bons et al, 2006) and cortical atrophy (Dhenain et al, 2000;Kraska et al, 2009) and it spontaneously develops numerous extracellular β-amyloid deposits in the cortical parenchyma (Bons et al, 1994;Mestre-Frances et al, 2000;Mestre-Frances et al, 1996). Rarely, neurofibrillary degeneration was observed in the cortical pyramidal neurons (Bons et al, 1991).…”

Attenuated effect of increased daylength on activity rhythm in the old mouse lemur, a non-human primate

“…Several of these studies indicate that daily and seasonal biological rhythms are altered in old mouse lemurs in ways that are remarkably similar to what is observed in human aging (Huang et al, 2002;Cayetanot et al, 2005): a decrease in amplitude of the locomotor activity level, an increased activity during the resting diurnal phase and an increase in fragmentation. For these and other reasons, the mouse lemur can be regarded as a model of primary importance for human aging (Bons et al, 2006).…”

Primate aging in the mammalian scheme: the puzzle of extreme variation in brain aging

“…The differences between general aging changes and clinical disease may be described as eugeric vs. pathogeric age changes (Finch 1972). For example, in US-wide samples of the NHANES, fluid intelligence scores peak at about 25 years and decline progressively at about a Chimpanzee, 41 years , 59 years (Gearing et al 1994(Gearing et al , 1996, and 2 "aged," no age given (Gearing et al 1994); gorilla, 44 years (Kimura et al 2001); orangutans-28, 31, and 36 years (Gearing et al 1997); baboon (Schultz et al 2000); and lemur (Bons et al 2006;Kraska et al 2011;Marchal et al 2012) 0.5%/year up through age 70 (McArdle 2009;Salthouse 2009). Complex multi-tasking ("walking while memorizing") also declines progressively across middle age (Li et al 2001).…”