Growth Associated Protein 43 (Gap-43) Predicts Brain Amyloidosis in Alzheimer’S Dementia Continuum: An [18 F] Av-45 Study Publisher Pubmed



Nemati R¹ ; Sohrabiashlaghi A² ; Saberian P³ ; Sadeghi M^{4, 5} ; Mardani S⁶ ; Abadi ASJH⁷ ; Yaghoobpoor A⁸ ; Heydari A⁹ ; Khoshroo N¹⁰ ; Rahnama Y⁴ ; Mayeli M⁴ ; Nasiri H¹¹ Show Affiliations
Source: BMC Neurology Published:2025

Abstract

Background: Growth-associated protein 43 (GAP-43) is a key protein involved in neuronal growth and synaptic plasticity. Alterations in GAP-43 levels have been associated with Alzheimer’s Disease (AD), potentially reflecting synaptic dysfunction. We evaluated the potential of GAP-43 as a biomarker for AD and explored its association with amyloid-beta (Aβ) levels, as well as its correlation with Aβ plaque burden in the brain. Methods: We screened 1,639 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. A total of 226 individuals met the eligibility criteria and were enrolled. Participants were classified into three groups: 77 cognitively normal (CN) individuals, 111 with mild cognitive impairment (MCI), and 38 with a diagnosis of AD. The associations between cerebrospinal fluid (CSF) GAP-43 levels with other biomarkers as well as [¹⁸F] AV-45 (Florbetapir) PET Standardized Uptake Value Ratios (SUVR) were investigated. Results: Our findings revealed significantly elevated CSF GAP-43 levels in individuals with AD compared to CN and MCI groups. Furthermore, GAP-43 levels showed a significant positive correlation with tau pathology. Notably, we observed a significant association between GAP-43 and [¹⁸F] Florbetapir PET SUVR in the MCI group, suggesting that GAP-43 may serve as a reliable biomarker in the early stages of AD. Conclusion: This study provides evidence supporting the role of GAP-43 as a potential biomarker for AD, particularly in relation to predicting the amyloid pathology pattern in the brain in the MCI stage. © The Author(s) 2025.