Cancer Chemotherapy Related Cognitive Impairment and the Impact of the Alzheimer’s Disease Risk Factor APOE

SIMPLE SUMMARY: Research into the causes and potential treatments for cancer-related cognitive impairment has increased greatly over the past several years. Advances have been made in studies related to human neuropsychology and animal models of behavior. Findings from both types of studies implicate a role of the genetic risk factor APOE4 in cancer-related cognitive impairment. APOE4 is the strongest genetic risk factor for Alzheimer’s disease, and this convergence across disparate research approaches now provides a great opportunity for insight into mechanisms of both conditions. This review provides an overview of potential mechanisms that could account for aspects of cancer-related cognitive impairment, and how they could be affected by the APOE genotype. ABSTRACT: Cancer related cognitive impairment (CRCI) is a serious impairment to maintaining quality of life in cancer survivors. Cancer chemotherapy contributes to this condition through several potential mechanisms, including damage to the blood brain barrier, increases in oxidative stress and inflammation in the brain, and impaired neurogenesis, each of which lead to neuronal dysfunction. A genetic predisposition to CRCI is the E4 allele of the Apolipoprotein E gene (APOE), which is also the strongest genetic risk factor for Alzheimer’s disease. In normal brains, APOE performs essential lipid transport functions. The APOE4 isoform has been linked to altered lipid binding, increased oxidative stress and inflammation, reduced turnover of neural progenitor cells, and impairment of the blood brain barrier. As chemotherapy also affects these processes, the influence of APOE4 on CRCI takes on great significance. This review outlines the main areas where APOE genotype could play a role in CRCI. Potential therapeutics based on APOE biology could mitigate these detrimental cognitive effects for those receiving chemotherapy, emphasizing that the APOE genotype could help in developing personalized cancer treatment regimens.