Establishing In-House Cutoffs of CSF Alzheimer’s Disease Biomarkers for the AT(N) Stratification of the Alzheimer Center Barcelona Cohort
Abstract
:1. Introduction
2. Results
2.1. Cutoffs of CSF Biomarkers for Both Immunoassays
2.2. Comparison of Immunoassays
2.3. Concordance between Immunoassays
2.4. MCI Progression in AT(N) Categories
3. Discussion
4. Methods
4.1. Participants
MCI Longitudinal Cohort
4.2. CSF Sampling and Analysis
4.3. Ethical Considerations
4.3.1. Study 1: Determination of Cutoff for Both Immunoassays
4.3.2. Study 2: Comparison of Immunoassays
4.3.3. Study 3: Concordance between Immunoassays
4.3.4. Study 4: MCI Progression
4.4. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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SCD | AD | Chi/T/UTest | p-Value | |
---|---|---|---|---|
n (%) | 45 (55%) | 37 (45%) | ||
Age, years | 65.6 ± 5.7 | 74.3 ± 8.4 | 5.35 | <0.0001 |
Gender, Female/Male (% Female) | 26/19 (58%) | 29/8 (78%) | 3.03 | 0.082 |
APOEε4 a +/− (%+) | 7/38 (16%) | 16/21 (43%) | 6.40 | 0.011 |
MMSE b score | 29.6 ± 0.7 | 20.7 ± 4.9 | 11.04 | <0.0001 |
Education, years (n = 79) | 13.0 ± 3.3 | 7.7 ± 4.0 | 6.41 | <0.0001 |
CSF biomarkers, ELISA | ||||
Aβ1-42, pg/mL | 1053 + 261 | 527 ± 112 | 36.00 | <0.0001 |
Aβ1-40, pg/mL (n = 72) | 11567 ± 3462 | 12216 ± 3566 | 578.00 | 0.443 |
t-Tau, pg/mL | 237 ± 79 | 726 ± 421 | 92.00 | <0.0001 |
P181Tau, pg/mL | 44 ± 12 | 100 ± 49 | 137.00 | <0.0001 |
Aβ1-42/Aβ1-40 (n = 72) | 0.096 ± 0.023 | 0.045 ± 0.012 | 32.00 | <0.0001 |
Aβ1-42/t-Tau | 4.93 ± 1.56 | 0.93 ± 0.49 | 5.00 | <0.0001 |
Aβ1-42/p181Tau | 25.50 ± 6.87 | 6.23 ± 2.5 | 4.00 | <0.0001 |
t-Tau/Aβ1-42 | 0.042 ± 0.015 | 0.1913 ± 0.091 | 5.00 | <0.0001 |
P181Tau/Aβ1-42 | 0.2248 ± 0.098 | 1.3938 ± 0.778 | 4.00 | <0.0001 |
CSF biomarkers, CLEIA | ||||
Aβ1-42, pg/mL | 1171 ± 395 | 568 ± 179 | 121.00 | <0.0001 |
Aβ1-40, pg/mL (n = 80) | 13093 ± 3654 | 14576 ± 4207 | 633.00 | 0.117 |
t-Tau, pg/mL | 300 ± 91 | 825 ± 431 | 80.50 | <0.0001 |
P181Tau, pg/mL (n = 80) | 40 ± 11 | 145 ± 87 | 48.00 | <0.0001 |
Aβ1-42/Aβ1-40 (n = 80) | 0.088 ± 0.014 | 0.039 ± 0.008 | 11.00 | <0.0001 |
Aβ1-42/t-Tau (n = 82) | 4.13 ± 1.36 | 0.81 ± 0.42 | 10.00 | <0.0001 |
Aβ1-42/p181Tau (n = 80) | 29.6 ± 8.1 | 4.9 ± 3.0 | 6.00 | <0.0001 |
t-Tau/Aβ1-42 (n = 82) | 0.27 ± 0.12 | 1.48 ± 0.6 | 10.00 | <0.0001 |
P181Tau/Aβ1-42 (n = 80) | 0.04 ± 0.01 | 0.25 ± 0.13 | 6.00 | <0.0001 |
Immunoassay | AUC c (95%IC) | Cutoff d | Youden J Index | Sensitivity | Specificity |
---|---|---|---|---|---|
Innotest ELISAe | |||||
Aβ1-42 | 0.98 (0.95–1.00) | <676 | 0.90 | 95 | 96 |
Aβ1-40 (n = 72) | 0.55 (0.42–0.69) | <10,530 | 0.16 | 77 | 40 |
t-Tau | 0.95 (0.89–0.99) | >367 | 0.80 | 87 | 93 |
p181Tau | 0.92 (0.85–0.98) | >58 | 0.72 | 81 | 91 |
Aβ1-42/Aβ1-40(n = 72) | 0.98 (0.95–1.00) | <0.069 | 0.89 | 97 | 92 |
Aβ1-42/t-Tau | 0.99 (0.99–1.00) | <2.13 | 0.95 | 97 | 98 |
Aβ1-42/p181Tau | 0.99 (0.99–1.00) | <13.73 | 0.98 | 100 | 98 |
Lumipulse CLEIAf | |||||
Aβ1-42 | 0.93 (0.88–0.98) | <796 | 0.72 | 92 | 80 |
Aβ1-40 (n = 80) | 0.60 (0.48–0.73) | <15,158 | 0.18 | 49 | 60 |
t-Tau | 0.95 (0.91–0.99) | >412 | 0.81 | 92 | 89 |
p181Tau (n = 80) | 0.97 (0.94–1.00) | >54 | 0.83 | 92 | 91 |
Aβ1-42/Aβ1-40 (n = 80) | 0.99 (0.98–1.00) | <0.063 | 0.95 | 100 | 95 |
Aβ1-42/t-Tau | 0.99 (0.98–1.00) | <1.37 | 0.95 | 95 | 100 |
Aβ1-42/p181Tau | 0.99 (0.99–1.00) | <11.55 | 0.97 | 97 | 100 |
ELISA | CLEIA | Kappa | CI 95% | Agreement (%) | |
---|---|---|---|---|---|
Negative | Positive | ||||
Aβ42 | |||||
Negative | 32 | 7 | 0.796 | 0.656–0.936 | 90 |
Positive | 0 | 29 | |||
t-Tau | |||||
Negative | 33 | 6 | 0.824 | 0.693–0.955 | 91 |
Positive | 0 | 29 | |||
p181Tau | |||||
Negative | 33 | 2 | 0.882 | 0.770–0.999 | 94 |
Positive | 2 | 31 | |||
Aβ42/Aβ40 | |||||
Negative | 25 | 0 | 0.629 | 0.461–0.79 | 81 |
Positive | 13 | 30 |
All MCIs | A-T-N- Normal | A+T-N- Amyloidosis | A-(TN)+ SNAPS | A+(TN)+ Prodromal AD | |
---|---|---|---|---|---|
n (%) | 647 | 190 (29.4) | 88 (13.6) | 125 (19.3) | 244 (37.7) |
Age, years (sd) | 72.8 (7.78) | 69.3 (9) | 72.4(7.6) | 73.8(7.1) | 75.1(6.1) |
Sex, (n, % Female) | 347 (53.6) | 98 (51.6) | 42 (47.7) | 68 (54.4) | 129 (57) |
APOEε4 carriers (%+) * | 32.7% | 12.7% | 33% | 26.8% | 53% |
Mean baseline MMSE score (sd) | 25.55 (3.2) | 26.3 (3.1) | 25.5 (3) | 25.8 (3.4) | 24.9 (3.3) |
Education mean years (s) | 8.1 (4.8) | 8.3 (4.2) | 8 (6.9) | 7.8 (4.6) | 8.1 (4.3) |
Follow-up time mean years (sd) | 1.75 (0.9) | 2.11 (0.9) | 1.64 (0.9) | 1.86 (0.9) | 1.44 (0.9) |
Dementia conversion rate n (%) | 234 (36.2) | 24 (12.6) | 37 (42) | 34 (27.2) | 139 (57) |
Non-AD conversions n (%) ** | 39 (16.7) | 15 (62.5) | 9 (24.3) | 11 (32.4) | 4 (2.9) |
ELISA/CLEIA/na (n) | 346/293/8 | 114/70/6 | 44/44/0 | 74/50/1 | 114/129/1 |
NPS clinical categories (n) *** | 107/25/283/223/9 | 49/7/98/33/3 | 15/3/42/27/1 | 25/3/52/42/3 | 18/12/91/121/2 |
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Orellana, A.; García-González, P.; Valero, S.; Montrreal, L.; de Rojas, I.; Hernández, I.; Rosende-Roca, M.; Vargas, L.; Tartari, J.P.; Esteban-De Antonio, E.; et al. Establishing In-House Cutoffs of CSF Alzheimer’s Disease Biomarkers for the AT(N) Stratification of the Alzheimer Center Barcelona Cohort. Int. J. Mol. Sci. 2022, 23, 6891. https://doi.org/10.3390/ijms23136891
Orellana A, García-González P, Valero S, Montrreal L, de Rojas I, Hernández I, Rosende-Roca M, Vargas L, Tartari JP, Esteban-De Antonio E, et al. Establishing In-House Cutoffs of CSF Alzheimer’s Disease Biomarkers for the AT(N) Stratification of the Alzheimer Center Barcelona Cohort. International Journal of Molecular Sciences. 2022; 23(13):6891. https://doi.org/10.3390/ijms23136891
Chicago/Turabian StyleOrellana, Adelina, Pablo García-González, Sergi Valero, Laura Montrreal, Itziar de Rojas, Isabel Hernández, Maitee Rosende-Roca, Liliana Vargas, Juan Pablo Tartari, Ester Esteban-De Antonio, and et al. 2022. "Establishing In-House Cutoffs of CSF Alzheimer’s Disease Biomarkers for the AT(N) Stratification of the Alzheimer Center Barcelona Cohort" International Journal of Molecular Sciences 23, no. 13: 6891. https://doi.org/10.3390/ijms23136891
APA StyleOrellana, A., García-González, P., Valero, S., Montrreal, L., de Rojas, I., Hernández, I., Rosende-Roca, M., Vargas, L., Tartari, J. P., Esteban-De Antonio, E., Bojaryn, U., Narvaiza, L., Alarcón-Martín, E., Alegret, M., Alcolea, D., Lleó, A., Tárraga, L., Pytel, V., Cano, A., ... Ruiz, A. (2022). Establishing In-House Cutoffs of CSF Alzheimer’s Disease Biomarkers for the AT(N) Stratification of the Alzheimer Center Barcelona Cohort. International Journal of Molecular Sciences, 23(13), 6891. https://doi.org/10.3390/ijms23136891