Volume 1449, Issue 1 p. 3-24
REVIEW

Alzheimer's disease and symbiotic microbiota: an evolutionary medicine perspective

Molly Fox

Corresponding Author

Molly Fox

Department of Anthropology, University of California Los Angeles, Los Angeles, California

Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California

Address for correspondence: Molly Fox, Ph.D., Department of Anthropology, University of California Los Angeles, 341 Haines Hall, 375 Portola Plaza, Los Angeles, CA 90095. [email protected]Search for more papers by this author
Delaney A. Knorr

Delaney A. Knorr

Department of Anthropology, University of California Los Angeles, Los Angeles, California

Both of these the authors contributed equally.

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Kacey M. Haptonstall

Kacey M. Haptonstall

Department of Ecology and Evolutionary Biology, University of California Los Angeles, Los Angeles, California

Both of these the authors contributed equally.

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First published: 10 June 2019
Citations: 38

Abstract

Microorganisms resident in our bodies participate in a variety of regulatory and pathogenic processes. Here, we describe how etiological pathways implicated in Alzheimer's disease (AD) may be regulated or disturbed by symbiotic microbial activity. Furthermore, the composition of symbiotic microbes has changed dramatically across human history alongside the rise of agriculturalism, industrialization, and globalization. We postulate that each of these lifestyle transitions engendered progressive depletion of microbial diversity and enhancement of virulence, thereby enhancing AD risk pathways. It is likely that the human life span extended into the eighth decade tens of thousands of years ago, yet little is known about premodern geriatric epidemiology. We propose that microbiota of the gut, oral cavity, nasal cavity, and brain may modulate AD pathogenesis, and that changes in the microbial composition of these body regions across history suggest escalation of AD risk. Dysbiosis may promote immunoregulatory dysfunction due to inadequate education of the immune system, chronic inflammation, and epithelial barrier permeability. Subsequently, proinflammatory agents—and occasionally microbes—may infiltrate the brain and promote AD pathogenic processes. APOE genotypes appear to moderate the effect of dysbiosis on AD risk. Elucidating the effect of symbiotic microbiota on AD pathogenesis could contribute to basic and translational research.

Competing interests

The authors declare no competing interests.