Level of CSF GAP-43 and white matter microstructural changes in Alzheimer's disease

Abstract

Objectives: Several studies have reported altered cerebrospinal fluid (CSF) concentrations of presynaptic proteins, such as growth-associated protein 43 (GAP-43) in Alzheimer's disease (AD) patients. Given the potential predictive role of CSF GAP-43 for AD, the current study aimed to investigate the relationship between CSF GAP-43 levels and DTI-detected microstructural changes in the white matter (WM).Methods: Data from three groups of participants including 39 control normals (CN), 138 MCI, and 39 AD subjects were obtained from the Alzheimer’s disease Neuroimaging Initiative (ADNI). Linear regression was used to the association of CSF-GAP43 and DTI values (including MD, RD, AxD, and FA) in the brain.Results: We found a significant association between CSF-GAP43 and FA (p-value = 0.011). Also, a negative association was found between CSF-GAP43 concentration and AD, MD, and RD values in MCI (p-value = 0.013, p-value = 0.004, p-value = 0.017). The regression models also revealed a positive association between CSF-GAP43 and FA value in AD subjects (p-value = 0.028). Furthermore, increased CSF-GAP43 level was associated with lower AD, MD, and RD values in brain WM of AD patients (p-value = 0.022, p-value = 0.033, p-value = 0.041).Conclusion: Our study provides a better understanding of the link between CSF GAP-43 and WM changes in patients with MCI and AD. Our findings support the application of CSF GAP-43 as an effective biomarker for monitoring individuals at high risk of AD in the early stages.

Keywords

• alzheimer’s disease
• white matter
• gap-43
• synaptic
• dti