The growth-associated protein 43 (GAP-43) is a presynaptic phosphoprotein in cerebrospinal fluid (CSF). The ε4 allele of apolipoprotein E (APOE) is an important genetic risk factor for Alzheimer's disease (AD). We aimed to evaluate the association of CSF GAP-43 with cognition and whether this correlation was related to the APOE ε4 status. We recruited participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, and they were divided into cognitively normal (CN) ε4 negative (CN ε4-), CN ε4 positive (CN ε4+), mild cognitive impairment (MCI) ε4 negative (MCI ε4-), MCI ε4 positive (MCI ε4+), AD ε4 negative (AD ε4-), and AD ε4 positive (AD ε4+) groups. Spearman's correlation was utilized to evaluate the relationship between CSF GAP-43 and core AD biomarkers at the baseline. We performed receiver-operating characteristic (ROC) curve analyses to investigate the diagnostic accuracy of CSF GAP-43. The correlations between CSF GAP-43 and the Mini-Mental State Examination (MMSE) scores and brain atrophy at baseline were assessed by using multiple linear regression, while the association between CSF GAP-43 and MMSE scores at the follow-up was tested by performing the generalized estimating equation (GEE). The role of CSF GAP-43 in the conversion from MCI to AD was evaluated using the Cox proportional hazard model. We found that the CSF GAP-43 level was significantly increased in MCI ε4+, AD ε4- and AD ε4+ groups compared with CN ε4- or MCI ε4- group. The negative associations between the CSF GAP-43 and MMSE scores at the baseline and follow-up were found in MCI ε4- and MCI ε4+ groups. In addition, baseline CSF GAP-43 was able to predict the clinical progression from MCI to AD. CSF GAP-43 may be a promising biomarker to screen cognition for AD. The effects of CSF GAP-43 on cognition were suspected to be relevant to APOE ε4 status.
Keywords: Alzheimer’s disease; Apolipoprotein E ε4; biomarker; growth-associated protein 43; synaptic loss.