Assessment of Lipid Peroxidation in Alzheimer’s Disease Differential Diagnosis and Prognosis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Participants
2.2. Lipid Peroxidation Compounds Determination and Samples Analysis
2.3. Statistical Analysis
3. Results
3.1. Patients’ Characteristics
3.2. Lipid Peroxidation Compounds
3.3. Multivariate Analysis
3.4. Alzheimer’s Disease Prognosis
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Clinical Evaluation | Classification of Participants | ||||
---|---|---|---|---|---|
Healthy | MCI-AD | MD-AD | AD-AD | Non-AD | |
β-Amyloid-42 (pg·mL−1) | >725 | <725 | <725 | <725 | >725 |
t-tau (pg·mL−1) | <485 | >485 | >485 | >485 | <485 |
p-tau (pg·mL−1) | <56 | >56 | >56 | >56 | <56 |
ADCS-ADL-MCI | >44 | <44 | <44 | <44 | <44 |
CDR | 0 | ≤0.5 | ≤1 | ≥2 | ≤1 |
FAQ | <9 | <9 | >9 | >9 | >9 |
MMSE | ≥27 | ≤27 | ≤27 | ≤27 | ≤27 |
RBANS.DM | ≥85 | ≤85 | ≤85 | ≤85 | ≤85 |
Variable | Healthy (n = 80) | MCI-AD (n = 106) | MD-AD (n = 70) | AD-AD (n = 11) | Non-AD (n = 20) | p Value (Kruskal-Wallis Test) | |
---|---|---|---|---|---|---|---|
Demographic characteristics | |||||||
Age (years, median (IQR)) | 63 (61–68) | 70 (67–74) | 71 (67–74) | 66 (70–73) | 65 (59–71) | <0.01 | |
Gender (female (%)) | 44 (55%) | 61 (57.5%) | 46 (65.7%) | 7 (63.6%) | 11 (55%) | 0.70 | |
Level of education n (%) | Basic Secondary University | 22 (27.5%) 21 (26.3%) 37 (46.3%) | 59 (55.7%) 23 (21.7%) 24 (22.6%) | 41 (58.6%) 16 (22.9%) 13 (18.6%) | 9 (81.8%) 1 (9.1%) 1 (9.1%) | 14 (70%) 3 (15%) 3 (15%) | <0.01 |
Clinical characteristics | |||||||
β-Amyloid-42 (pg·mL−1, median (IQR)) | 1201 (942.75–1439.75) | 597 (471.05–709.07) | 574 (444.75–648.50) | 636 (601.76–708.88) | 982 (858–1647) | <0.01 | |
t-tau (pg·mL−1, median (IQR)) | 224 (173.25–304) | 583 (432.50–773.50) | 621 (448.50–945.50) | 699 (473–936) | 289 (205–376) | <0.01 | |
p-tau (pg·mL−1, median (IQR)) | 36 (28–47.25) | 90 (70.50–109.50) | 88.50 (73–144) | 95 (73–122) | 40 (32–61) | <0.01 | |
ADCS-ADL-MCI (median (IQR)) | 47 (43–50.75) | 41 (31–46) | 36 (24–42) | 29.50 (3–34.50) | 29 (22.50–40.75) | <0.01 | |
CDR (median (IQR)) | 0 (0–0) | 0.5 (0.5–0.5) | 1 (0.5–1) | 2 (2–3) | 1 (0.5–1) | <0.01 | |
FAQ (median (IQR)) | 0 (0–2) | 4 (1–7) | 13 (10–17.25) | 21 (14–25) | 11.50 (8–21) | <0.01 | |
MMSE (median (IQR)) | 29 (28–30) | 25 (22–27.25) | 20 (17.75–24) | 14 (12–19) | 23 (18–25) | <0.01 | |
RBANS.DM (median (IQR)) | 100 (95–106) | 52 (40–75) | 40 (40–49) | 40 (40–44) | 58 (45–78) | <0.01 |
Variable (nmol·L−1) | Healthy (n = 80) Median (1st, 3rd Quartile) | MCI-AD (n = 106) Median (1st, 3rd Quartile) | MD-AD (n = 70) Median (1st, 3rd Quartile) | AD-AD (n = 11) Median (1st, 3rd Quartile) | Non-AD (n = 20) Median (1st, 3rd Quartile) | p Value (Kruskal-Wallis Test) | |
---|---|---|---|---|---|---|---|
PGs a | PGE2 | 0.27 (0.05–0.45) | 0.07 (0–0.35) | 0.12 (0.04–0.50) | 0.10 (0–0.20) | 0.10 (0.07–0.16) | 0.03 * |
PGF2α | 0.55 (0.28–0.86) | 0.60 (0.10–0.85) | 0.63 (0.26–1.13) | 0.60 (0.30–0.80) | 0.88 (0.53–1.38) | 0.058 ^ | |
15-E2t-IsoP | 0.78 (0.27–1.56) | 0.31 (0.09–1.01) | 0.30 (0.07–1.08) | 0.25 (0–0.67) | 0.13 (0.05–0.29) | <0.01 * | |
15-F2t-IsoP | 0.03 (0.01–0.06) | 0.02 (0–0.05) | 0.03 (0–0.21) | 0.02 (0–0.03) | 0 (0–0.57) | 0.08 | |
IsoPs a | 15(R)-15-F2t-IsoP | 0.31 (0.20–0.59) | 0.30 (0.16–0.53) | 0.35 (0.20–0.58) | 0.25 (0.06–0.45) | 0.48 (0.21–0.75) | 0.21 |
2,3-dinor-15-epi-15-F2t-IsoP | 0 (0–0.02) | 0 (0–0) | 0 (0–0) | 0 (0–0) | 0 (0–0) | 0.58 | |
15-keto-15-E2t-IsoP | 0.33 (0–0.92) | 0 (0–0.17) | 0.01 (0–0.25) | 0 (0–0.32) | 0.05 (0–0.38) | <0.01 * | |
15-keto-15-F2t-IsoP | 0.37 (0.17–0.67) | 0.25 (0.07–0.40) | 0.33 (0.15–0.56) | 0.27 (0.07–0.40) | 0.47 (0.30–0.78) | <0.01 * | |
5-F2t-IsoP | 1.38 (0.88–2.62) | 0.98 (0.33–1.69) | 1.25 (0.65–2.00) | 0.65 (0.35–1.45) | 1.98 (1.08–2.55) | <0.01 * | |
Total IsoPs | 0.72 (0.31–1.39) | 0.39 (0.26–0.67) | 0.45 (0.30–0.68) | 0.27 (0.22–0.37) | 0.62 (0.44–0.79) | <0.01 * | |
IsoFs a | Total IsoFs | 0.33 (0.08–0.46) | 0.14 (0.08–0.32) | 0.19 (0.09–0.36) | 0.08 (0.05–0.14) | 0.23 (0.19–0.40) | <0.01 * |
NeuroPs b | 4(RS)-4-F4t-NeuroP | 1.37 (0.95–3.68) | 1.10 (0–1.50) | 1.08 (0.58–1.40) | 0.97 (0–1.27) | 1.03 (0.61–1.46) | <0.01 * |
10-epi-10-F4t-NeuroP | 0.15 (0.06–0.22) | 0.13 (0.01–0.22) | 0.20 (0.05–0.32) | 0.11 (0.07–0.20) | 0.32 (0.25–0.41) | <0.01 * | |
14(RS)-14-F4t-NeuroP | 1.08 (0.13–1.89) | 0.53 (0–1.58) | 0.88 (0.25–1.30) | 0.15 (0–0.42) | 0.91 (0.60–1.43) | 0.01 * | |
Total NeuroPs | 0.05 (0–0.56) | 0 (0–0.11) | 0 (0–0.05) | 0 (0–0.38) | 0.01 (0–0.06) | <0.01 * | |
NeuroFs b | Total NeuroFs | 0.16 (0.06–0.32) | 0.15 (0.05–0.33) | 0.12 (0.05–0.25) | 0.09 (0–0.11) | 0.08 (0.04–0.15) | 0.02 * |
Dihomo-IsoPs c | 1a,1b-dihomo-PGF2α | 0 (0–3.34) | 0 (0–0) | 0 (0–1.03) | 0 (0–0) | 1.18 (0–1.40) | <0.01 * |
Ent-7(RS)-7-F2t-dihomo-IsoP | 0.03 (0–0.17) | 0.10 (0–0.22) | 0.15 (0.10–0.22) | 0.15 (0.05–0.22) | 0.12 (0.10–0.19) | <0.01 * | |
17-F2t-dihomo-IsoP | 0 (0–0) | 0 (0–0) | 0 (0–0) | 0 (0–0) | 0 (0–0) | 0.10 | |
17-epi-17-F2t-dihomo-IsoP | 0 (0–0) | 0 (0–0.02) | 0 (0–0.02) | 0 (0–0.02) | 0 (0–0) | 0.054 ^ | |
Dihomo-IsoFs c | 17(RS)-10-epi-SC-Δ15-11-dihomo-IsoF | 0 (0–0) | 0 (0–0) | 0 (0–0) | 0 (0–0) | 0 (0–0) | 0.07 |
7(RS)-ST-Δ8-11-dihomo-IsoF | 0 (0–0.22) | 0 (0–0.17) | 0.02 (0–0.10) | 0.05 (0.02–0.12) | 0 (0–0.09) | 0.52 |
Lipids | Healthy vs. MCI-AD | Healthy vs. MD-AD | Healthy vs. AD-AD | Healthy vs. Non-AD | MCI-AD vs. MD-AD | MCI-AD vs. AD-AD | MCI-AD vs. Non-AD | MD-AD vs. AD-AD | MD-AD vs. Non-AD | |
---|---|---|---|---|---|---|---|---|---|---|
PGs a | PGE2 | <0.01 * | 0.38 | 0.06 | 0.23 | 0.05 * | 0.78 | 0.23 | 0.23 | 0.90 |
PGF2α | 0.66 | 0.30 | 0.97 | <0.01 * | 0.16 | 0.79 | <0.01 * | 0.50 | 0.09 | |
15-E2t-IsoP | <0.01 * | <0.01 * | 0.01 * | <0.01 * | 0.99 | 0.37 | 0.09 | 0.52 | 0.09 | |
15-F2t-IsoP | 0.07 | 0.24 | 0.10 | 0.59 | 0.01 * | 0.89 | 0.95 | 0.18 | 0.26 | |
IsoPs a | 15(R)-15-F2t-IsoP | 0.65 | 0.51 | 0.21 | 0.20 | 0.20 | 0.23 | 0.07 | 0.12 | 0.31 |
2,3-dinor-15-epi-15-F2t-IsoP | 0.48 | 0.19 | 0.40 | 0.22 | 0.46 | 0.61 | 0.40 | 0.91 | 0.73 | |
15-keto-15-E2t-IsoP | <0.01 * | <0.01 * | 0.03 * | 0.11 | 0.08 | 0.57 | 0.11 | 0.79 | 0.73 | |
15-keto-15-F2t-IsoP | <0.01 * | 0.42 | 0.19 | 0.18 | 0.02 * | 0.76 | <0.01 * | 0.35 | 0.05 * | |
5-F2t-IsoP | <0.01 * | 0.06 | 0.01 * | 0.31 | 0.16 | 0.47 | <0.01 * | 0.10 | 0.01 * | |
Total IsoPs | <0.01 * | 0.01 * | <0.01 * | 0.49 | 0.33 | 0.02 * | 0.01 * | <0.01 * | 0.09 | |
IsoFs a | Total IsoFs | <0.01 * | 0.051 ^ | <0.01 * | 0.63 | 0.21 | 0.01 * | 0.02 * | <0.01 * | 0.18 |
NeuroPs b | 4(RS)-4-F4t-NeuroP | <0.01 * | <0.01 * | 0.02 * | 0.02 * | 0.95 | 0.38 | 0.98 | 0.35 | 0.92 |
10-epi-10-F4t-NeuroP | 0.72 | 0.18 | 0.55 | <0.01 * | 0.10 | 0.73 | <0.01 * | 0.34 | <0.01 * | |
14(RS)-14-F4t-NeuroP | 0.059 ^ | 0.26 | <0.01 * | 0.99 | 0.26 | 0.07 | 0.17 | <0.01 * | 0.49 | |
Total NeuroPs | <0.01 * | <0.01 * | 0.15 | 0.28 | 0.73 | 0.98 | 0.34 | 0.98 | 0.12 | |
NeuroFs b | Total NeuroFs | 0.73 | 0.39 | <0.01 * | 0.04 * | 0.58 | <0.01 * | 0.054 ^ | 0.02 * | 0.14 |
Dihomo-IsoPs c | 1a,1b-dihomo-PGF2α | <0.01 * | <0.01 * | <0.01 * | 0.78 | 0.26 | 0.14 | <0.01 * | 0.06 | <0.01 * |
Ent-7(RS)-7-F2t-dihomo-IsoP | 0.01 * | <0.01 * | 0.08 | 0.02 * | 0.01 * | 0.57 | 0.51 | 0.60 | 0.35 | |
17-F2t-dihomo-IsoP | 0.56 | 0.04 * | 0.51 | 0.06 | 0.08 | 0.42 | 0.13 | 0.21 | 0.82 | |
17-epi-17-F2t-dihomo-IsoP | <0.01 * | <0.01 * | 0.26 | 0.48 | 0.65 | 0.82 | 0.36 | 0.68 | 0.27 | |
Dihomo-IsoFs c | 17(RS)-10-epi-SC-Δ15-11-dihomo-IsoF | 0.64 | 0.059 ^ | 0.59 | 0.02 * | 0.09 | 0.51 | 0.04 * | 0.27 | 0.53 |
7(RS)-ST-Δ8-11-dihomo-IsoF | 0.89 | 0.83 | 0.38 | 0.21 | 0.92 | 0.22 | 0.28 | 0.19 | 0.24 |
Parameter | (95% CI) |
---|---|
Sensitivity (%) | 81.3 (75.1–86.2) |
Specificity (%) | 64 (54.2–72.7) |
Accuracy (%) | 75.3 (70–80) |
Positive predictive value (%) | 81 (74.6–85.8) |
Negative predictive value (%) | 64.6 (54.8–73.4) |
Odds ratio | 7.72 (4.46–13.37) |
Lipids | p Value (Kruskal-Wallis Test) | |
---|---|---|
PGs a | PGE2 | 0.11 |
PGF2α | 0.36 | |
15-E2t-IsoP | 0.71 | |
15-F2t-IsoP | 0.03 * | |
IsoPs a | 15(R)-15-F2t-IsoP | 0.17 |
2,3-dinor-15-epi-15-F2t-IsoP | 0.71 | |
15-keto-15-E2t-IsoP | 0.22 | |
15-keto-15-F2t-IsoP | 0.08 | |
5-F2t-IsoP | 0.19 | |
Total IsoPs | 0.02 * | |
IsoFs a | Total IsoFs | 0.01 * |
NeuroPs b | 4(RS)-4-F4t-NeuroP | 0.65 |
10-epi-10-F4t-NeuroP | 0.23 | |
14(RS)-14-F4t-NeuroP | 0.03 * | |
Total NeuroPs | 0.94 | |
NeuroFs b | Total NeuroFs | 0.03 * |
Dihomo-IsoPs c | 1a,1b-dihomo-PGF2α | 0.13 |
Ent-7(RS)-7-F2t-dihomo-IsoP | 0.06 | |
17-F2t-dihomo-IsoP | 0.13 | |
17-epi-17-F2t-dihomo-IsoP | 0.86 | |
Dihomo-IsoFs c | 17(RS)-10-epi-SC-Δ15-11-dihomo-IsoF | 0.15 |
7(RS)-ST-Δ8-11-dihomo-IsoF | 0.43 |
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Ferré-González, L.; Peña-Bautista, C.; Baquero, M.; Cháfer-Pericás, C. Assessment of Lipid Peroxidation in Alzheimer’s Disease Differential Diagnosis and Prognosis. Antioxidants 2022, 11, 551. https://doi.org/10.3390/antiox11030551
Ferré-González L, Peña-Bautista C, Baquero M, Cháfer-Pericás C. Assessment of Lipid Peroxidation in Alzheimer’s Disease Differential Diagnosis and Prognosis. Antioxidants. 2022; 11(3):551. https://doi.org/10.3390/antiox11030551
Chicago/Turabian StyleFerré-González, Laura, Carmen Peña-Bautista, Miguel Baquero, and Consuelo Cháfer-Pericás. 2022. "Assessment of Lipid Peroxidation in Alzheimer’s Disease Differential Diagnosis and Prognosis" Antioxidants 11, no. 3: 551. https://doi.org/10.3390/antiox11030551