Role of nerve growth factor on cognitive impairment in patients with Alzheimer's disease carrying apolipoprotein E 4

Aims To investigate the roles of neurotrophic factors on cognition in patients with Alzheimer's disease (AD) carrying Apolipoprotein E (APOE) epsilon 4.Methods Totals of 173 patients with AD were divided into APOE epsilon 4 carrier and non-carrier groups, and their demographics, cognition, and neurotrophic factors in cerebrospinal fluid (CSF) were compared. Multiple linear regression analyses were performed to assess correlations among APOE epsilon 4, neurotrophic factors and cognition. Mediation analyses were conducted to assess the sequential associations among APOE epsilon 4, nerve growth factor (NGF), and cognition.Results Global cognition and multiple domains were impaired in the APOE epsilon 4 carrier group (all p < 0.05). NGF level in the APOE epsilon 4 carrier group was lower than that in the non-carrier group (p = 0.016). NGF level showed significant correlations with both global and multiple domains cognitions. Specifically, NGF mediated the association between APOE epsilon 4 and Animal Fluency Test score (beta, -0.45; 95% CI [-0.96, -0.07]; p < 0.001) and Trail Making Test-A (time) (beta, 0.15; 95% CI [0.01, 0.33]; p < 0.001).Conclusion APOE epsilon 4 is associated with cognitive impairment, and those carrying APOE epsilon 4 have decreased NGF level in CSF. Declined NGF level is correlated with compromised cognition. NGF mediates APOE epsilon 4-associated cognitive impairment.