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Cerebrospinal fluid growth-associated protein 43 levels in patients with progressive and stable mild cognitive impairment

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Abstract

Background

Cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) is prominently elevated in Alzheimer’s disease (AD) dementia patients in comparison to normal controls. CSF GAP-43 levels in mild cognitive impairment (MCI) individuals who have different clinical trajectories need to be studied.

Methods

We examined 137 cognitively normal (CN) controls, 218 stable MCI patients (sMCI), 99 progressive MCI (pMCI) patients, and 120 AD dementia patients. Associations between the CSF GAP-43 levels and the four diagnosis groups were evaluated with multiple-variable linear regression. The relationships between CSF GAP-43 and core CSF biomarkers were assessed by Spearman correlations. Cox regression analysis was performed to assess the values of GAP-43 in predicting MCI conversion. We examined associations between baseline CSF GAP-43 levels and longitudinal cognitive function, hippocampal volumes, and brain glucose metabolism using linear mixed-effects models.

Results

CSF GAP-43 was elevated in the pMCI and AD groups in comparison to the CN group and in the pMCI and AD groups in comparison to the sMCI group. CSF GAP-43 significantly predicted conversion from MCI to AD. CSF GAP-43 was a significant predictor of cognitive decline, hippocampal atrophy, and brain hypometabolism over time. Furthermore, elevated CSF GAP-43 levels were associated with accelerated deterioration in cognition and neurodegeneration.

Conclusions

CSF GAP-43 is increased in the predementia stage of AD, and it may enhance the neurodegenerative process. Future efforts on pharmacological interventions targeting synaptic dysfunction could be promising in AD treatment.

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Data availability

The data sets analyzed during the current study are available upon request with no restriction.

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Acknowledgements

Data collection and sharing for this project were sponsored by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012).

Funding

We do not have any financial support for this study.

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Authors and Affiliations

  1. Department of Neurology and Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing, 100053, China

    Yuanyuan Lu

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  1. Yuanyuan Lu
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Correspondence to Yuanyuan Lu.

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Since the data in this paper were obtained from the ADNI, it does not include any research involving human or animal subjects.

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Data used to prepare this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wpcontent/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

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Lu, Y., for the Alzheimer’s Disease Neuroimaging Initiative. Cerebrospinal fluid growth-associated protein 43 levels in patients with progressive and stable mild cognitive impairment. Aging Clin Exp Res 34, 2399–2406 (2022). https://doi.org/10.1007/s40520-022-02202-z

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  • DOI: https://doi.org/10.1007/s40520-022-02202-z

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