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. 2025 Apr 1;25(1):134.
doi: 10.1186/s12883-025-04140-5.

Growth associated protein 43 (GAP-43) predicts brain amyloidosis in Alzheimer's dementia continuum: an [18 F] AV-45 study

Rezvan Nemati  1 , Ahmadreza Sohrabi-Ashlaghi  2 , Parsa Saberian  3 , Mohammad Sadeghi  4   5 , Sajjad Mardani  6 , Amir Sina Jafari Hossein Abadi  7 , Ali Yaghoobpoor  8 , Atefeh Heydari  9 , Niloofar Khoshroo  10 , Yassin Rahnama  4 , Mahsa Mayeli  4 , Hamide Nasiri  11
Affiliations

Growth associated protein 43 (GAP-43) predicts brain amyloidosis in Alzheimer's dementia continuum: an [18 F] AV-45 study

Rezvan Nemati et al. BMC Neurol. .

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.

Keywords: Alzheimer’s disease; Growth associated protein 43; Mild cognitive impairment; Positron emission tomography.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The institutional review boards of all participating centers approved the study procedure ( https://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf ), and all participants or their authorized representatives provided written informed consent. Ethics approval was obtained from the institutional review boards of each institution involved: Oregon Health and Science University; University of Southern California; University of California—San Diego; University of Michigan; Mayo Clinic, Rochester; Baylor College of Medicine; Columbia University Medical Center; Washington University, St. Louis; University of Alabama at Birmingham; Mount Sinai School of Medicine; Rush University Medical Center; Wien Center; Johns Hopkins University; New York University; Duke University Medical Center; University of Pennsylvania; University of Kentucky; University of Pittsburgh; University of Rochester Medical Center; University of California, Irvine; University of Texas Southwestern Medical School; Emory University; University of Kansas, Medical Center; University of California, Los Angeles; Mayo Clinic, Jacksonville; Indiana University; Yale University School of Medicine; McGill University, Montreal-Jewish General Hospital; Sunnybrook Health Sciences, Ontario; U.B.C. Clinic for AD & Related Disorders; and Cognitive Neurology—St. Joseph’s, Ontario; Cleveland Clinic Lou Ruvo Center for Brain Health; Northwestern University; Premiere Research Inst (Palm Beach Neurology); Georgetown University Medical Center; Brigham and Women’s Hospital; Stanford University; Banner Sun Health Research Institute; Boston University; Howard University; Case Western Reserve University; University of California, Davis—Sacramento; Neurological Care of CNY; Parkwood Hospital; University of Wisconsin; University of California, Irvine—BIC; Banner Alzheimer’s Institute; Dent Neurologic Institute; Ohio State University; Albany Medical College; Hartford Hospital, Olin Neuropsychiatry Research Center; Dartmouth-Hitchcock Medical Center; Wake Forest University Health Sciences; Rhode Island Hospital; Butler Hospital; UC San Francisco; Medical University South Carolina; St. Joseph’s Health Care Nathan Kline Institute; University of Iowa College of Medicine; and Cornell University and University of South Florida: USF Health Byrd Alzheimer’s Institute. This study was conducted using ADNI data. The ADNI study is ethically approved and operated in accordance with the Declaration of Helsinki, 1964. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Receiver operating characteristic (ROC) curves for CSF biomarkers GAP-43, Aβ42, T-tau, and P-tau in differentiating cognitive groups. Abbreviations: MCI vs. CN (A). AD vs. MCI (B). AD vs. MCI (C). CN: cognitively normal; MCI: mild cognitive impairment; T-tau: total tau; P-tau: phosphorylated tau; Aβ: amyloid-β
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