Abstract
BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia, characterized by a considerable decline in memory. The aggregation of amyloid-beta (Aβ) plaques and tau tangles is the primary pathology of AD. Recently, growth-associated protein 43 (GAP-43) has been suggested as a reliable biomarker in the early diagnosis of patients with AD continuum. OBJECTIVES: In this study, we aimed to observe the association of white matter (WM) features detected by diffusion tensor imaging (DTI) with the cerebrospinal fluid (CSF) level of GAP-43 in patients with cognitive impairment. METHODS: Information from 132 participants from different ATN groups, including 62 with A-/TN-, 16 with A+/TN-, 30 with A-/TN+, and 24 with A+/TN + pathology were enrolled from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We observed the association of CSF GAP-43 with DTI findings among patients with AD spectrum by using a linear regression model adjusted for age, sex, period of education, and APOE ε4 status. RESULTS: Our findings suggested a significant association for CSF GAP-43 concentration with WM features in the inferior cerebellar peduncle in the A-/TN- group as well as WM in the cerebral peduncle, anterior corona radiata, and the left sagittal stratum of patients with A+/TN- pathology. In addition, a significant relation was reported between DTI findings in the cingulum cingulate, fornix, body, and splenium of the corpus callosum of patients with A-/TN + with CSF GAP-43 concentration. A similar significant association was shown in the posterior limb of the internal capsule of the A+/TN + group. Moreover, a significant association was found between CSF level of GAP-43 and the performance of A+/TN + and A+/TN-groups in cognitive tests. CONCLUSIONS: Our study observed a significant association between CSF GAP-43 concentration and WM microstructural findings in different brain tracts of patients with various ATN groups, suggesting GAP-43 as a reliable and accurate biomarker in the early detection of patients with cognitive decline. Further longitudinal investigations with other imaging methods can provide more evidence on the role of GAP-43 in the detection of brain damage among patients with AD spectrum.