Higher Plasma Amyloid-β Levels Are Associated with a Higher Risk of Cancer: A Population-Based Prospective Cohort Study

Abstract

Various studies show an inverse relation between Alzheimer disease and cancer, but findings are likely to be biased by surveillance and survival bias. Plasma amyloid-β (Aβ) is defined as a preclinical feature of Alzheimer disease, with lower levels of Aβ42 being associated with a higher risk of Alzheimer disease. To get more insight into the biological link between Alzheimer disease and cancer, we investigated plasma Aβ levels in relation to the risk of cancer. Between 2002 and 2005, we measured plasma Aβ40 and Aβ42 levels in 3,949 participants from the population-based Rotterdam Study. These participants were followed until the onset of cancer, all-cause dementia, death, loss to follow-up, or January 1, 2014, whichever came first. We used Cox proportional hazards models to investigate the association between plasma Aβ40 and Aβ42 levels, and the risk of cancer. Analyses were stratified by cancer site. During a median (interquartile range) follow-up of 9.0 years (6.9-10.1), 560 participants were diagnosed with cancer. Higher levels of log2 plasma Aβ40 and Aβ42 were associated with a higher risk of cancer [hazard ratio per standard deviation increase for Aβ40 = 1.12 (95% confidence interval, CI = 1.02-1.23) and Aβ42 = 1.12 (95% CI = 1.03-1.23)]. These effect estimates were most pronounced for hematologic cancers, urinary tract cancers, and cancers of unknown primary origin. We found that higher levels of both plasma Aβ40 and Aβ42 were associated with a higher risk of cancer. Our study suggests a potential biological link between Alzheimer disease and cancer. The pathophysiologic role of Aβ in cancer and its causality warrant further investigation.