Association of CSF GAP-43 and APOE ε4 with Cognition in Mild Cognitive Impairment and Alzheimer’s Disease
Abstract
:1. Background
2. Methods
2.1. ADNI Database Description
2.2. Participants and Classification Criteria
2.3. CSF Measurements
2.4. Neuroimaging Methods and Cognitive Assessments
2.5. Statistical Methods
3. Results
3.1. CSF GAP-43 Levels in Different Diagnostic Groups
3.2. Characteristics of Included Participants
3.3. Correlations of CSF GAP-43 Levels with CSF Core AD Biomarkers
3.4. Diagnostic Ability of CSF GAP-43 and CSF Core AD Biomarkers
3.5. Cross-Sectional Correlations of CSF GAP-43 with MMSE, Hippocampus Volumes, and Ventricular Volumes
3.6. Longitudinal Associations between Baseline CSF GAP-43 and MMSE Progression
3.7. Ability of CSF GAP-43 to Predict Future Cognitive Impairment
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Baseline Characteristics | CN ε4– (n = 169) | CN ε4+ (n = 69) | MCI ε4– (n = 204) | MCI ε4+ (n = 184) | AD ε4– (n = 40) | AD ε4+ (n = 78) | p Value |
---|---|---|---|---|---|---|---|
Age (years) | 73 ± 9 d | 71 ± 9 e | 72 ± 11 e | 71 ± 11 a,e,f | 77 ± 13 b,c,d | 74.5 ± 10 d | <0.001 |
Female, N (%) | 86 (50.9%) | 44 (63.8%) e | 93 (45.6%) | 81 (44.0%) | 12 (30.0%) b | 35 (44.9%) | 0.013 |
Education (years) | 16 ± 3 | 17 ± 2 | 16 ± 4 | 16 ± 4 | 16 ± 4 | 16 ± 4 | 0.131 |
MMSE | 29 ± 2 c,d,e,f | 29 ± 1 c,d,e,f | 29 ± 1 a,b,e,f | 28 ± 3 a,b,e,f | 23 ± 3 a,b,c,d | 24 ± 3 a,b,c,d | <0.001 |
CSF Aβ42 (pg/mL) | 215 ± 63 b,d,e,f | 159 ± 74.5 a,c,f | 205 ± 82 b,d,e,f | 140.5 ± 51.5 a,c,f | 148 ± 59.5 a,c,f | 124.5 ± 29.3 a,b,c,d,e | <0.001 |
CSF T-tau (pg/mL) | 54.2 ± 31.5 d,e,f | 63.8 ± 41.2 d,e,f | 56.7 ± 41.5 d,e,f | 89.75 ± 75 a,b,c,f | 106 ± 71.5 a,b,c | 120 ± 75.2 a,b,c,d | <0.001 |
CSF P-tau (pg/mL) | 27.5 ± 19.8 b,d,e,f | 37.5 ± 24.3 a,c,f | 28.6 ± 21.9 b,d,e,f | 42.25 ± 30.1 a,c | 41.25 ± 32.6 a,c | 54.7 ± 32.6 a,b,c | <0.001 |
CN ε4− | CN ε4+ | MCI ε4− | MCI ε4+ | AD ε4− | AD ε4+ | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
rs | p | rs | p | rs | p | rs | p | rs | p | rs | p | |
Aβ42 | 0.078 | 0.312 | 0.056 | 0.649 | −0.094 | 0.180 | −0.306 | <0.001 | 0.379 | 0.016 | −0.078 | 0.498 |
T-tau | 0.711 | <0.001 | 0.709 | <0.001 | 0.751 | <0.001 | 0.742 | <0.001 | 0.453 | 0.003 | 0.696 | <0.001 |
P-tau | 0.579 | <0.001 | 0.576 | <0.001 | 0.581 | <0.001 | 0.611 | <0.001 | 0.227 | 0.158 | 0.509 | <0.001 |
GAP-43 | Aβ42 | T-tau | P-tau | GAP-43 and Aβ42 | T-tau and Aβ42 | P-tau and Aβ42 | |
---|---|---|---|---|---|---|---|
CN ε4+ | 0.627 (0.548−0.705) (p = 0.002) | 0.776 (0.706−0.847) (p < 0.001) | 0.664 (0.585−0.743) (p < 0.001) | 0.708 (0.634−0.782) (p < 0.001) | 0.778 (0.708−0.849) (p < 0.001) | 0.782 (0.714−0.850) (p < 0.001) | 0.789 (0.722−0.856) (p < 0.001) |
MCI ε4- | 0.586 (0.528−0.644) (p = 0.004) | 0.603 (0.546−0.660) (p = 0.001) | 0.582 (0.524−0.639) (p = 0.007) | 0.582 (0.524−0.639) (p = 0.007) | 0.608 (0.551−0.666) (p < 0.001) | 0.602 (0.545−0.659) (p = 0.001) | 0.603 (0.546−0.660) (p = 0.001) |
MCI ε4+ | 0.686 (0.631−0.741) (p < 0.001) | 0.879 (0.843−0.915) (p < 0.001) | 0.825 (0.783−0.868) (p < 0.001) | 0.785 (0.738−0.832) (p < 0.001) | 0.880 (0.844−0.916) (p < 0.001) | 0.901 (0.870−0.933) (p < 0.001) | 0.888 (0.854−0.922) (p < 0.001) |
AD ε4- | 0.700 (0.606−0.795) (p < 0.001) | 0.828 (0.754−0.902) (p < 0.001) | 0.855 (0.792−0.918) (p < 0.001) | 0.780 (0.700−0.861) (p < 0.001) | 0.850 (0.779−0.920) (p < 0.001) | 0.890 (0.830−0.951) (p < 0.001) | 0.851 (0.781−0.921) (p < 0.001) |
AD ε4+ | 0.695 (0.625−0.765) (p < 0.001) | 0.937 (0.903−0.972) (p < 0.001) | 0.889 (0.848−0.931) (p < 0.001) | 0.847 (0.796−0.898) (p < 0.001) | 0.939 (0.905−0.973) (p < 0.001) | 0.956 (0.929−0.982) (p < 0.001) | 0.948 (0.917−0.979) (p < 0.001) |
CN ε4- | CN ε4+ | MCI ε4- | MCI ε4+ | AD ε4- | AD ε4+ | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
β (95% CI) | p | β (95% CI) | p | β (95% CI) | p | β (95% CI) | p | β (95% CI) | p | β (95% CI) | p | |
Cross-sectional (MLR) | ||||||||||||
MMSE | 0.069 (−0.082, 0.221) | 0.368 | 0.176 (−0.052, 0.403) | 0.128 | −0.148 (−0.280, −0.015) | 0.029 | −0.179 (−0.321, −0.037) | 0.014 | −0.281 (−0.617, 0.056) | 0.099 | 0.179 (−0.041, 0.399) | 0.109 |
Bilateral hippocampal volume | −0.117 (−0.227, −0.008) | 0.036 | 0.033 (−0.199, 0.265) | 0.775 | −0.036 (−0.150, 0.078) | 0.535 | −0.026 (−0.146, 0.093) | 0.663 | −0.276 (−0.546, −0.006) | 0.045 | −0.027 (−0.207, 0.152) | 0.762 |
Ventricular volume | −0.287 (−0.426, −0.147) | <0.001 | −0.163 (−0.393, 0.067) | 0.161 | −0.139 (−0.263, −0.016) | 0.027 | −0.279 (−0.401, −0.158) | <0.001 | −0.283 (−0.597, 0.032) | 0.076 | −0.228 (−0.430, −0.027) | 0.027 |
Longitudinal (GEE) | ||||||||||||
MMSE progression | - | - | - | - | −0.197 (−0.372, −0.022) | 0.027 | −0.151 (−0.289, −0.013) | 0.032 | - | - | - | - |
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Zhu, Y.; Guo, X.; Zhu, F.; Zhang, Q.; Yang, Y.; for the Alzheimer’s Disease Neuroimaging Initiative. Association of CSF GAP-43 and APOE ε4 with Cognition in Mild Cognitive Impairment and Alzheimer’s Disease. Cells 2023, 12, 13. https://doi.org/10.3390/cells12010013
Zhu Y, Guo X, Zhu F, Zhang Q, Yang Y, for the Alzheimer’s Disease Neuroimaging Initiative. Association of CSF GAP-43 and APOE ε4 with Cognition in Mild Cognitive Impairment and Alzheimer’s Disease. Cells. 2023; 12(1):13. https://doi.org/10.3390/cells12010013
Chicago/Turabian StyleZhu, Yueli, Xiaoming Guo, Feng Zhu, Qin Zhang, Yunmei Yang, and for the Alzheimer’s Disease Neuroimaging Initiative. 2023. "Association of CSF GAP-43 and APOE ε4 with Cognition in Mild Cognitive Impairment and Alzheimer’s Disease" Cells 12, no. 1: 13. https://doi.org/10.3390/cells12010013
APA StyleZhu, Y., Guo, X., Zhu, F., Zhang, Q., Yang, Y., & for the Alzheimer’s Disease Neuroimaging Initiative. (2023). Association of CSF GAP-43 and APOE ε4 with Cognition in Mild Cognitive Impairment and Alzheimer’s Disease. Cells, 12(1), 13. https://doi.org/10.3390/cells12010013