Association of CSF GAP-43 and APOE 4 with Cognition in Mild Cognitive Impairment and Alzheimer's Disease

The growth-associated protein 43 (GAP-43) is a presynaptic phosphoprotein in cerebrospinal fluid (CSF). The epsilon 4 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 epsilon 4 status. We recruited participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, and they were divided into cognitively normal (CN) epsilon 4 negative (CN epsilon 4-), CN epsilon 4 positive (CN epsilon 4+), mild cognitive impairment (MCI) epsilon 4 negative (MCI epsilon 4-), MCI epsilon 4 positive (MCI epsilon 4+), AD epsilon 4 negative (AD epsilon 4-), and AD epsilon 4 positive (AD epsilon 4+) 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 epsilon 4+, AD epsilon 4- and AD epsilon 4+ groups compared with CN epsilon 4- or MCI epsilon 4- group. The negative associations between the CSF GAP-43 and MMSE scores at the baseline and follow-up were found in MCI epsilon 4- and MCI epsilon 4+ 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 epsilon 4 status.