Growth Associated Protein 43 (GAP-43) predicts brain amyloidosis in Alzheimer’s Dementia Continuum: an [18F] AV45 study

Background Alzheimer's disease (AD) is a global health concern with a rising prevalence. Growth Associated Protein 43 (GAP-43) is a crucial protein for neuronal growth and synaptic plasticity, essential for maintaining healthy brain function. In AD, changes in GAP-43 levels have been observed, potentially indicating synaptic dysfunction and neurodegeneration. This study investigates the potential of GAP-43 as a biomarker in AD by analyzing its correlation with amyloid-beta (Aβ) pathology, a hallmark feature of the disease using [18F] AV45. Methods We examined 1639 participants using a dataset extracted from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Results A total of 226 subjects meeting the eligibility criteria were recruited from the ADNI dataset for enrollment. These individuals were categorized into three groups: 77 cognitively normal (CN) individuals, 111 with mild cognitive impairment (MCI), and 38 AD. Our results reveal elevated CSF GAP-43 levels in AD, and GAP-43 exhibited a stronger association with tau pathology than with Aβ. The study establishes a robust positive correlation between GAP-43 and [18F] florbetapir PET ([18F] AV45), a marker for Aβ plaques, independent of cognitive status. Additionally, logistic regression identified GAP-43) as significant predictors of AD. Conclusion The diagnostic accuracy of [18F] AV45, combined with GAP-43, enhances understanding of AD pathology. This study sets the stage for future research on GAP-43's trajectory in disease progression and the molecular mechanisms linking GAP-43 and amyloid-beta. The findings suggest promising avenues for novel therapeutic targets, contributing to advancements in early detection and treatment strategies for AD.