Olfactory impairment in men and mice related to aging and amyloid-induced pathology

Abstract

Olfaction, or the sense of smell, is one of the most ancient senses in men and mice, important for a large variety of innate and acquired behaviors. Clinical data reveal an early impairment of olfaction during normal aging and in the course of neurodegenerative diseases, but the underlying cellular/molecular mechanisms remain obscure. In the current review, we compare different aspects of the aging- and Alzheimer's disease related impairment of olfaction in men and mice, aiming at the identification of common morbidities and biomarkers, which can be analyzed in detail in the appropriate mouse models. We also identify common, often interdependent (patho)physiological pathways, including but not limited to extracellular amyloid depositions, neuroinflammation, ɛ4 allele of the apolipoprotein E, CNS insulin resistance, and the impairment of adult neurogenesis, to be targeted by basic and clinical research.

Keywords: Alzheimer’s disease; Amyloid plaques; Normal aging; Odor identification; Olfaction; Olfactory memory.

Fig. 1

Prevalence of olfactory impairment in participants of different age and sex. Figure is adapted from refs. [143, 145]

Fig. 2

Summary of the known olfactory impairments during normal aging and the development of AD. a Human data showing at which age the decline in the given ability occurs, compared to young adult subjects. b Human data showing at which age the AD-related decline in the given ability occurs. Here, in contrast to panel a, NEC subjects serve as a reference. Because of the lack of reliable longitudinal studies of the mentioned capabilities, the arrows in the given graph reflect the age of the cohort under study rather than the true age when the given impairment appears. Data are taken from refs. [41, 43, 44, 68, 78, 96, 97, 117, 128, 143, 144]. Y-axis is shown in arbitrary units