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Environmental Factor

Environmental Factor

Your Online Source for NIEHS News

March 2017

Dementia shows gene-environment link, loss of smell is early sign

NIEHS-funded scientists report dementia risk from gene variant plus air pollution, and impaired sense of smell may be an early warning sign.

Dementia is linked to air pollution exposures combined with a certain genetic variation, and an impaired sense of smell may serve as an early warning sign in both black and white older adults, according to new studies funded in part by NIEHS. These findings provide public health experts with new insights to help battle Alzheimer’s disease (AD) and dementia.

Jiu-Chiuan Chen, M.D., Sc.D., from the NIEHS-funded Southern California Environmental Health Sciences Center at the University of Southern California (USC), led a team of scientists that reported the first evidence, from both humans and mice, that neurological effects of airborne fine particulate matter — less than 2.5 microns in diameter, or PM2.5 — may involve gene-environment interactions. The study was published Jan. 31 in the journal Translational Psychiatry.

A second study, published Dec. 30, 2016 in the journal Neurology, reported that in a biracial group of older adults, lower ability to identify odors was associated with significantly greater risk of developing dementia in later years (see sidebar).

“This work validates the use of odor identification as a simple, inexpensive and highly sensitive marker of risk for preclinical dementia among older adults,” said lead author Kristine Yaffe, M.D., from the University of California at San Francisco, in a press release. The research team included Honglei Chen, M.D., Ph.D., who was with the NIEHS Epidemiology Branch at the time of the research and is now at Michigan State University.

Gene variant worsens air pollution impact

The USC researchers found that U.S. women living in areas with high levels of particulate matter were 92 percent more likely to develop dementia, including AD. The effects were strongest in women with a gene variant known as APOE epsilon4, or APOEe4 — a known risk factor for AD, especially in women. Yet the gene accounts for less than 50 percent of heritable risk. So the scientists looked for a connection with environmental exposures.

To learn more about the mechanisms of particulate matter’s effects on the brain and its neurons, the team studied female mice. “The experimental data showed that exposure of mice to air particles collected [near a local freeway] on the edge of USC damaged neurons in the hippocampus, the memory center that is vulnerable to both brain aging and Alzheimer’s disease,” Chen said in a USC press release. The researchers want to extend their studies to men and male mice.

These novel findings were featured in a Jan. 26 story in Science Magazine about air pollution and the brain. Neruoscience news writer Emily Underwood addressed the implications, if these results hold up in the general population. “And if real, the air pollution connection would give public health experts a tool for sharply lowering Alzheimer’s risks — a welcome prospect for a disease that is so devastating and that, for now, remains untreatable,” Underwood wrote. According to the authors of the new study, traffic emissions account for one-fourth of all PM2.5 in outdoor air worldwide.

“The genetic insights from this study are important,” said Jonathan Hollander, Ph.D., who oversees NIEHS grants related to Parkinson’s disease and neurodevelopmental toxicology. He was not involved in the research. “They help explain associations that have been observed between air pollution, such as near-roadway pollution, and increased risk of cognitive decline.”

Cacciottolo M, Wang X, Driscoll I, Woodward N, Saffari A, Reyes J, Serre ML, Vizuete W, Sioutas C, Morgan TE, Gatz M, Chui HC, Shumaker SA, Resnick SM, Espeland MA, Finch CE, Chen JC. 2017. Particulate air pollutants, APOE alleles and their contributions to cognitive impairment in older women and to amyloidogenesis in experimental models. Transl Psychiatry 7(1):e1022.

Yaffe K, Freimer D, Chen H, Asao K, Rosso A, Rubin S, Tranah G, Cummings S, Simonsick E. 2016. Olfaction and risk of dementia in a biracial cohort of older adults. Neurology 88(5):456–462.

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