Higher plasma amyloid-beta levels are associated with a higher risk of cancer: a population-based prospective cohort study

Background Various studies show an inverse relation between Alzheimer disease (AD) 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 AD, with lower levels of Aβ42 being associated with a higher risk of AD. To get more insight into the biological link between AD and cancer, we investigated plasma Aβ levels in relation to the risk of cancer. Methods 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 for the onset of cancer, all-cause dementia, death, loss to follow-up, or January 1st, 2014, whichever came first. We used Cox proportional hazard models to investigate the association between plasma Aβ40 and Aβ42 levels, and the risk of cancer. Analyses were stratified by cancer site. Results 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%CI=1.02;1.23] and Aβ42=1.12 [95%CI=1.03;1.23]). These effect estimates were most pronounced for hematological cancers, urinary tract cancers, and cancers of unknown primary origin. Conclusions We found that higher levels of both plasma Aβ40 and Aβ42 were associated with a higher risk of cancer. Impact Our study suggests a potential biological link between AD and cancer. The pathophysiological role of Aβ in cancer and its causality warrant further investigation.