Association of Growth-Associated Protein 43 with White Matter Alterations in Patients with Cognitive Decline

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.

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.

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.

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.

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.