CSF GAP-43 as a biomarker of synaptic dysfunction is associated with tau pathology in Alzheimer’s disease
Abstract To test whether cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) concentration is elevated in Alzheimer’s disease (AD) dementia and its associations with other hallmarks of AD, we examined the CSF GAP-43 measurements of 787 participants (245 cognitively normal (CN), 415 indiv...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-10-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-20324-2 |
| _version_ | 1797986051927572480 |
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| author | Qiang Qiang Loren Skudder-Hill Tomoko Toyota Wenshi Wei Hiroaki Adachi |
| author_facet | Qiang Qiang Loren Skudder-Hill Tomoko Toyota Wenshi Wei Hiroaki Adachi |
| author_sort | Qiang Qiang |
| collection | DOAJ |
| description | Abstract To test whether cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) concentration is elevated in Alzheimer’s disease (AD) dementia and its associations with other hallmarks of AD, we examined the CSF GAP-43 measurements of 787 participants (245 cognitively normal (CN), 415 individuals with mild cognitive impairment (MCI) and 127 individuals with AD dementia) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. Associations were investigated between CSF GAP-43 and clinical diagnosis, Aβ/tau/neurodegeneration (AT(N)) status, CSF and blood biomarkers of AD, cognitive measurements and brain neuroimaging findings. CSF GAP-43 levels were increased in patients with AD dementia (mean, 6331.05 pg/ml) compared with the CN (mean, 5001.05 pg/ml) and MCI (mean, 5118.8 pg/ml) (P < 0.001) groups. CSF GAP-43 correlated with CSF phosphorylated tau 181(p-tau) (r = 0.768, P < 0.001), and had high diagnostic accuracy in differentiating tau positive status vs. tau negative status (area under the receiver operating characteristic curve, 0.8606). CSF GAP-43 was particularly elevated among individuals with tau positive status. High CSF GAP-43 was associated with longitudinal deterioration of cognitive scores and brain neuroimaging findings. CSF GAP-43 was associated with a clinical diagnosis of AD dementia and with an individual’s tau status, cognitive measurements and findings from neuroimaging. This study implies that CSF GAP-43 as a biomarker of synaptic dysfunction could predict the disease progression of AD patients. |
| first_indexed | 2024-04-11T07:26:56Z |
| format | Article |
| id | doaj.art-dc793755a69e49eab88f91fcf82ea6da |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T07:26:56Z |
| publishDate | 2022-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-dc793755a69e49eab88f91fcf82ea6da2022-12-22T04:37:02ZengNature PortfolioScientific Reports2045-23222022-10-0112111010.1038/s41598-022-20324-2CSF GAP-43 as a biomarker of synaptic dysfunction is associated with tau pathology in Alzheimer’s diseaseQiang Qiang0Loren Skudder-Hill1Tomoko Toyota2Wenshi Wei3Hiroaki Adachi4Department of Neurology, Cognitive Disorders Center, Huadong Hospital, Fudan UniversityYuquan Hospital, Tsinghua University School of Clinical MedicineDepartment of Neurology, University of Occupational and Environmental Health School of MedicineDepartment of Neurology, Cognitive Disorders Center, Huadong Hospital, Fudan UniversityDepartment of Neurology, University of Occupational and Environmental Health School of MedicineAbstract To test whether cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) concentration is elevated in Alzheimer’s disease (AD) dementia and its associations with other hallmarks of AD, we examined the CSF GAP-43 measurements of 787 participants (245 cognitively normal (CN), 415 individuals with mild cognitive impairment (MCI) and 127 individuals with AD dementia) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. Associations were investigated between CSF GAP-43 and clinical diagnosis, Aβ/tau/neurodegeneration (AT(N)) status, CSF and blood biomarkers of AD, cognitive measurements and brain neuroimaging findings. CSF GAP-43 levels were increased in patients with AD dementia (mean, 6331.05 pg/ml) compared with the CN (mean, 5001.05 pg/ml) and MCI (mean, 5118.8 pg/ml) (P < 0.001) groups. CSF GAP-43 correlated with CSF phosphorylated tau 181(p-tau) (r = 0.768, P < 0.001), and had high diagnostic accuracy in differentiating tau positive status vs. tau negative status (area under the receiver operating characteristic curve, 0.8606). CSF GAP-43 was particularly elevated among individuals with tau positive status. High CSF GAP-43 was associated with longitudinal deterioration of cognitive scores and brain neuroimaging findings. CSF GAP-43 was associated with a clinical diagnosis of AD dementia and with an individual’s tau status, cognitive measurements and findings from neuroimaging. This study implies that CSF GAP-43 as a biomarker of synaptic dysfunction could predict the disease progression of AD patients.https://doi.org/10.1038/s41598-022-20324-2 |
| spellingShingle | Qiang Qiang Loren Skudder-Hill Tomoko Toyota Wenshi Wei Hiroaki Adachi CSF GAP-43 as a biomarker of synaptic dysfunction is associated with tau pathology in Alzheimer’s disease Scientific Reports |
| title | CSF GAP-43 as a biomarker of synaptic dysfunction is associated with tau pathology in Alzheimer’s disease |
| title_full | CSF GAP-43 as a biomarker of synaptic dysfunction is associated with tau pathology in Alzheimer’s disease |
| title_fullStr | CSF GAP-43 as a biomarker of synaptic dysfunction is associated with tau pathology in Alzheimer’s disease |
| title_full_unstemmed | CSF GAP-43 as a biomarker of synaptic dysfunction is associated with tau pathology in Alzheimer’s disease |
| title_short | CSF GAP-43 as a biomarker of synaptic dysfunction is associated with tau pathology in Alzheimer’s disease |
| title_sort | csf gap 43 as a biomarker of synaptic dysfunction is associated with tau pathology in alzheimer s disease |
| url | https://doi.org/10.1038/s41598-022-20324-2 |
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