Plasma Proteomic Biomarkers in Alzheimer’s Disease and Cardiovascular Disease: A Longitudinal Study
Abstract
:1. Introduction
2. Results
2.1. Baseline Descriptive Statistics
2.2. Multivariable LMM Analysis
2.3. Correlation Analysis and Variable Cluster Analysis
3. Discussion
3.1. Proteomic Biomarkers Associated with AD, CVDs, and APOE-ε4
3.2. Proteomic Biomarkers Associated with MCI, CVDs, and APOE-ε4
3.3. Proteomic Biomarkers Associated with AD, MCI, CVDs, and APOE-ε4
3.4. Relationship among Shared Proteomic Biomarkers
3.5. Strengths and Limitations
4. Materials and Methods
4.1. Dataset
4.2. Measures
4.3. Statistical Methods
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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Variable | AD | MCI | CN | F/χ2, p | CVD | Non-CVD | t/χ2, p |
---|---|---|---|---|---|---|---|
Age (mean ± SD) | 74.8 ± 8.1 | 74.8 ± 7.7 | 75.1 ± 5.8 | 0.05, 0.9527 | 75.2 ± 7.2 | 73.9 ± 7.8 | 3.60, 0.0584 |
Gender | |||||||
Male | 65 | 248 | 30 | 4.39, 0.1113 | 258 | 85 | 4.38, 0.0364 * |
Female | 46 | 135 | 28 | 140 | 69 | ||
Education (mean ± SD) | 15.1 ± 3.2 | 15.6 ± 3.0 | 15.7 ± 2.8 | 1.31, 0.2699 | 15.4 ± 3.1 | 15.8 ± 2.8 | 1.70, 0.1930 |
APOE- ε4 | |||||||
0 | 36 | 178 | 53 | 54.80, <0.0001 *** | 187 | 80 | 1.10, 0.2953 |
1+ | 75 | 205 | 5 | 211 | 74 |
Variable | AD vs. CN (t, p) | MCI vs. CN (t, p) | CVD vs. Non-CVD (t, p) | APOE-ε4-1+ vs. 0 (t, p) | 12 Months (t, p) |
---|---|---|---|---|---|
A1Micro | 2.40, 0.0168 * | 1.80, 0.0720 | 4.68, <0.0001 *** | −2.01, 0.0454 * | −5.20, <0.0001 *** |
ApoH | 2.20, 0.0279 * | −1.55, 0.1225 | 2.90, 0.0039 ** | −0.54, 0.5874 | −15.40, <0.0001 *** |
β2M | 3.10, 0.0020 ** | 0.28, 0.7813 | 4.52, <0.0001 *** | −2.61, 0.0092 ** | −0.97, 0.3314 |
BNP | 5.53, <0.0001 *** | 4.94, <0.0001 *** | 3.82, 0.0001 ** | −0.40, 0.6866 | 3.728, 0.0011 ** |
Complement C3 | 2.66, 0.0080 ** | −1.44, 0.1504 | 2.07, 0.0391 * | −2.30, 0.0221 * | 2.94, 0.0034 ** |
Cystatin C | 2.31, 0.0213 * | −1.24, 0.2157 | 5.78, <0.0001 *** | −2.49, 0.0130 * | −1.65, 0.1001 |
KIM1 | −3.06, 0.0023 ** | 0.74, 0.4617 | 3.12, 0.0019 ** | 0.01, 0.9900 | −5.47, <0.0001 *** |
NGAL | 2.83, 0.0048 ** | 0.60, 0.5465 | 2.53, 0.0117 * | −1.61 0.1080 | −3.94, <0.0001 *** |
PPP | 3.53, 0.0005 ** | 3.08, 0.0022 ** | 2.15, 0.0322 * | 1.31, 0.1904 | 2.77, 0.0059 ** |
TFF3 | 2.84, 0.0046 ** | 0.30, 0.7653 | 4.30, <0.0001 *** | −1.37, 0.1706 | 4.09, <0.0001 *** |
THP | −3.51, 0.0005 ** | −2.91, 0.0038 ** | −4.10, <0.0001 *** | 2.90, 0.0038 ** | −9.98, <0.0001 *** |
TIM1 | 3.29, 0.0011 ** | 0.68, 0.4999 | 2.14, 0.0328 * | −1.51, 0.1321 | 0.72, 0.4744 |
TM | 2.14, 0.0324 * | 0.90, 0.3665 | 4.19, <0.0001 *** | −0.74, 0.4626 | −1.46, 0.1455 |
VEGF | 3.63, 0.0003 ** | 2.40, 0.0169 * | 4.13, <0.0001 *** | −1.70, 0.0895 | 1.92, 0.0553 |
Variable | AD vs. CN (t, p) | MCI vs. CN (t, p) | CVD vs. non-CVD (t, p) | APOE-ε4-1+ vs. 0 (t, p) | 12 Months (t, p) |
---|---|---|---|---|---|
ApoD | −1.84, 0.0670 | −3.12, 0.0019 ** | −2.00, 0.0456 * | −0.92, 0.3576 | −0.78, 0.4374 |
AXL | 1.62, 0.1067 | 2.64, 0.0084 ** | 2.28, 0.0233 * | −0.25, 0.8027 | −5.62, <0.0001 *** |
Calcitonin | 1.86, 0.0633 | 2.75, 0.0061 ** | 2.17, 0.0302 * | 2.51, 0.0124 * | −2.34, 0.0197 * |
CD40 | 1.15, 0.2498 | −2.61, 0.0093 ** | −0.93, 0.3543 | −0.42, 0.6278 | 2.97, 0.0032 ** |
C-peptide | 1.14, 0.2558 | 2.03, 0.0429 * | 4.77, <0.0001 *** | 0.22, 0.8281 | 1.05, 0.2947 |
pM | 0.56, 0.5784 | 2.10, 0.0365 * | 3.63, 0.0003 ** | −1.15, 0.2525 | 1.95, 0.0517 |
TNFR2 | 0.64, 0.5208 | −2.07, 0.0385 * | 3.96, <0.0001 *** | −2.38, 0.0175 * | −3.43, 0.0007 ** |
TTR | −1.42, 0.1562 | −3.69, 0.0002 ** | 2.68, 0.0075 ** | 1.10, 0.2701 | −10.65, <0.0001 *** |
Comparison | Visit | Difference ± SE | t, p |
---|---|---|---|
AD vs. CN | Baseline | −0.52 ± 0.16 | −3.16, 0.0048 ** |
12 months | −0.60 ± 0.16 | −3.66, 0.0008 ** | |
MCI vs. CN | Baseline | −0.31 ± 0.14 | −2.22, 0.0695 |
12 months | −0.50 ± 0.14 | −3.53, 0.0013 ** | |
AD vs. MCI | Baseline | −0.20 ± 0.10 | −1.97, 0.1219 |
12 months | −0.10 ± 0.11 | −0.99, 0.5863 | |
CVD vs. non-CVD | Baseline | −0.39 ± 0.09 | −4.32, <0.0001 *** |
12 months | −0.33 ± 0.09 | −3.55, 0.0004 ** | |
APOE-ε4-1+ vs. 0 | Baseline | 0.24 ± 0.09 | 2.73, 0.0066 ** |
12 months | 0.26 ± 0.09 | 2.94, 0.0034 ** |
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Theeke, L.A.; Liu, Y.; Wang, S.; Luo, X.; Navia, R.O.; Xiao, D.; Xu, C.; Wang, K.; The Alzheimer and Disease Neuroimaging Initiative. Plasma Proteomic Biomarkers in Alzheimer’s Disease and Cardiovascular Disease: A Longitudinal Study. Int. J. Mol. Sci. 2024, 25, 10751. https://doi.org/10.3390/ijms251910751
Theeke LA, Liu Y, Wang S, Luo X, Navia RO, Xiao D, Xu C, Wang K, The Alzheimer and Disease Neuroimaging Initiative. Plasma Proteomic Biomarkers in Alzheimer’s Disease and Cardiovascular Disease: A Longitudinal Study. International Journal of Molecular Sciences. 2024; 25(19):10751. https://doi.org/10.3390/ijms251910751
Chicago/Turabian StyleTheeke, Laurie A., Ying Liu, Silas Wang, Xingguang Luo, R. Osvaldo Navia, Danqing Xiao, Chun Xu, Kesheng Wang, and The Alzheimer and Disease Neuroimaging Initiative. 2024. "Plasma Proteomic Biomarkers in Alzheimer’s Disease and Cardiovascular Disease: A Longitudinal Study" International Journal of Molecular Sciences 25, no. 19: 10751. https://doi.org/10.3390/ijms251910751