LEXINGTON, Ky. — Researchers at the University of Kentucky Sanders-Brown Center on Aging have discovered that a single genetic variant may influence the risk of two major diseases — dementia and cancer — but in opposite ways, according to findings recently published in the Journal of Neuropathology & Experimental Neurology.

The study indicates that a particular variation in the GRN gene is associated with an increased risk of LATE, a common form of age-related dementia, while also being linked to a lower risk of cancer. The discovery could help explain a long-observed scientific mystery: why dementia and cancer occur together less often than expected.

"For years, researchers around the world have observed that individuals with dementia seem less likely to develop cancer, while people with cancer appear less likely to develop dementia," said Yuriko Katsumata, Ph.D., associate professor in the UK College of Medicine and investigator at the Sanders-Brown Center on Aging. "Our findings suggest there may be a biological explanation for that relationship and that the GRN gene could be one important piece of the puzzle."

The study builds on previous work by Sanders-Brown researchers, including Erin L. Abner, Ph.D., and David W. Fardo, Ph.D., who have investigated the inverse relationship between cancer and Alzheimer's disease. Earlier research using autopsy data found that cancer history was associated with lower levels of Alzheimer's disease-related brain pathology.

The GRN gene encodes a protein called progranulin, which plays important roles throughout the body and has been linked to both cancer and neurodegenerative diseases. Higher levels of progranulin have been associated with cancer growth, while lower levels have been linked to the buildup of abnormal proteins associated with LATE, short for limbic-predominant age-related TDP-43 encephalopathy.

LATE is a recently characterized type of dementia that typically affects individuals over age 80. It causes problems with memory and thinking but has different underlying causes than Alzheimer's disease, characterized by the buildup of TDP-43 protein rather than amyloid plaques and tau tangles.

Khine Zin Aung, Ph.D., a postdoctoral researcher at Sanders-Brown and first author of the study, said the findings could have significant implications for future therapies. The research was led in part by Pete Nelson, M.D., Ph.D., director of the neuropathology core at Sanders-Brown, who previously led an international working group that first defined LATE as a distinct disease entity.