Role of nerve growth factor on cognitive impairment in patients with Alzheimer's disease carrying apolipoprotein E ε4

CNS Neurosci Ther. 2023 Dec 19. doi: 10.1111/cns.14560. Online ahead of print.


Aims: To investigate the roles of neurotrophic factors on cognition in patients with Alzheimer's disease (AD) carrying Apolipoprotein E (APOE) ε4.

Methods: Totals of 173 patients with AD were divided into APOE ε4 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 ε4, neurotrophic factors and cognition. Mediation analyses were conducted to assess the sequential associations among APOE ε4, nerve growth factor (NGF), and cognition.

Results: Global cognition and multiple domains were impaired in the APOE ε4 carrier group (all p < 0.05). NGF level in the APOE ε4 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 ε4 and Animal Fluency Test score (β, -0.45; 95% CI [-0.96, -0.07]; p < 0.001) and Trail Making Test-A (time) (β, 0.15; 95% CI [0.01, 0.33]; p < 0.001).

Conclusion: APOE ε4 is associated with cognitive impairment, and those carrying APOE ε4 have decreased NGF level in CSF. Declined NGF level is correlated with compromised cognition. NGF mediates APOE ε4-associated cognitive impairment.

Keywords: Alzheimer's disease; apolipoprotein E ε4; cognitive function; nerve growth factor; neurotrophic factors.