Biomonitoring of Mycotoxins in Plasma of Patients with Alzheimer’s and Parkinson’s Disease
Abstract
:1. Introduction
2. Results and Discussion
2.1. LC-MS/MS Analysis
2.2. Plasma Samples
2.3. Presence of Mycotoxins
2.4. Statistical Analysis
3. Conclusions
4. Materials and Methods
4.1. Reagents
4.2. Subjects
4.3. Plasma Collection
4.4. Sample Preparation
4.5. LC/MS-MS Analysis
4.6. Analytical Method Validation
4.7. Statistical Analysis and Data Handling
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
15-ADON | 15-acetyldeoxynivalenol |
3-ADON | 3-acetyldeoxynivalenol |
Aβ | amyloid beta |
ACN | acetonitrile |
AD | Alzheimer´s disease |
AFB1 | aflatoxin B1 |
AFB2 | aflatoxin B2 |
AFG1 | aflatoxin G1 |
AFG2 | aflatoxin G2 |
AFM1 | aflatoxin M1 |
CIRS | chronic inflammatory response syndrome |
CNT | control |
DAS | diacetoxyscirpenol |
DOM-1 | deepoxy-deoxynivalenol |
DON | deoxynivalenol |
FUS-X | fusarenon-X |
GDS | Global Deterioration Scale |
HBM | human biomonitoring |
HY | Hoehn and Yahr |
LC | liquid chromatography |
LC-MS/MS | liquid chromatography coupled to mass spectrometry in tandem |
LOD | limit of detection |
LOQ | limit of quantification |
NEO | neosolaniol |
NIV | nivalenol |
OTA | ochratoxin A |
OTA-d5 | ochratoxin A-(phenyl-d5) |
OTB | ochratoxin B |
PD | Parkinson´s disease |
q | transition of qualification |
Q | transition of quantification |
QqQ | triple quadrupole |
RE | relative error of the mean |
SD | standard deviation |
STER | sterigmatocystin |
ZEA | zearalenone |
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Groups/ Sub Groups | Disease Stage | N° of Subjects (M/W *) | Age Range (Years) |
---|---|---|---|
Subjects | 93 (43/50) | 43–85 | |
Control (CNT) | 25 (8/17) | 43–81 | |
Patients | 68 (35/33) | 44–85 | |
PD | 44 (29/15) | 44–85 | |
PD sub-group 1. | HY scale: 1–2 | 35 (23/12) | 44–85 |
PD sub-group 2 | HY scale: 2.5–3 | 9 (6/3) | 62–83 |
AD | GDS scale 3–7 | 24 (6/18) | 60–85 |
Before Enzymatic Treatment | After Enzymatic Treatment | |||
---|---|---|---|---|
OTA | OTB | OTA | STER | |
Total population | ||||
Positive samples (N/%) | 72 (77%) | 12 (13%) | 66 (89%) | 65 (88%) |
Mean value (M/W); ng/mL | 1.77 (2.10/1.50) | 0.07 (0.10/0.04) | 2.00 (1.86/2.10) | 0.81 (0.78/0.84) |
Median (M/W); ng/mL | 1.65 (1.92/1.47) | 0 (0/0) | 1.68 (1.52/1.93) | 0.87 (0.86/0.88) |
Range (min-max); ng/mL | 0–8.81 | 0–0.75 | 0–6.45 | 0–2.20 |
Control (CNT) | ||||
Positive samples (N/%) | 23 (92%) | 6 (24%) | 19 (86%) | 16 (73%) |
Mean value (M/W); ng/mL | 2.15 (2.47/1.99) | 0.12 (0.22/0.07) | 2.51 (2.11/2.69) | 0.51 (0.53/0.51) |
Median (M/W); ng/mL | 1.56 (2.19/1.50) | 0 (0.22/0) | 2.35 (2.01/2.41) | 0.65 (0.69/0.63) |
Range (min-max); ng/mL | 0–8.81 | 0–0.75 | 0–6.25 | 0–0.90 |
Patients | ||||
Positive samples (N/%) | 49 (72%) | 6 (9%) | 47 (90%) | 49 (94%) |
Mean value (M/W); ng/mL | 1.64 (2.01/1.24) | 0.05 (0.07/0.02) | 1.78 (1.79/1.76) | 0.94 (0.84/1.02) |
Median (M/W); ng/mL | 1.66 (1.92/1.45) | 0 (0/0) | 1.46 (1.46/1.43) | 0.94 (0.87/0.97) |
Range (min-max); ng/mL | 0–6.44 | 0–0.71 | 0–6.45 | 0–2.22 |
Patients with PD | ||||
Positive samples (N/%) | 33 (75%) | 6 (14%) | 31 (91%) | 31 (91%) |
Mean value (M/W); ng/mL | 1.93 (2.13/1.54) | 0.07 (0.09/0.05) | 1.88 (1.82/1.99) | 0.90 (0.82/1.04) |
Median (M/W); ng/mL | 1.86 (1.98/1.50) | 0 (0/0) | 1.53 (1.41/1.61) | 0.95 (0.87/1.02) |
Range (min-max); ng/mL | 0–6.44 | 0–0.71 | 0–6.45 | 0–1.31 |
Patients with AD | ||||
Positive samples (N/%) | 16 (67%) | 0 (0%) | 16 (89%) | 18 (100%) |
Mean value (M/W); ng/mL | 1.11 (1.47/0.99) | 0 (0/0) | 1.59 (1.64/1.57) | 1.01 (0.98/1.02) |
Median (M/W); ng/mL | 1.46 (1.75/1.45) | 0 (0/0) | 1.39 (1.96/1.37) | 0.91 (0.92/0.91) |
Range (min-max); ng/mL | 0–2.11 | 0 | 0–3.94 | 0.74–2.20 |
OTA | STER | |
---|---|---|
CNT/patient group (PD + AD) | - | <0.0001 |
CNT/PD/AD | 0.0447 | 0.0001 |
CNT/PD | - | <0.0001 |
CNT/AD | - | <0.0001 |
PD/AD | 0.0114 | - |
M/W | 0.0014 | - |
M/W in patient group (PD + AD) | 0.0013 | - |
M/W in patient group PD | (0.0613) | 0.0304 |
Sex = M in CNT/PD/AD | - | 0.0128 |
Sex = M in CNT/patient group (PD + AD) | - | 0.0047 |
Sex = M in CNT/PD | - | 0.0105 |
Sex = M in CNT/AD | - | 0.0080 |
Sex = W in CNT/PD/AD | - | 0.0001 |
Sex = W in CNT/patient group (PD + AD) | - | 0.0001 |
Sex = W in CNT/PD | - | <0.0001 |
Sex = W in CNT/AD | - | <0.0001 |
OTA | STER | |||||
---|---|---|---|---|---|---|
rho | p-Value | N° Observations | rho | p-Value | N° Observations | |
Age | −0.2033 | 0.0507 | 93 | 0.2686 | 0.0207 | 74 |
Age in PD | −0.3304 | 0.0285 | 44 | - | - | - |
Age in men | −0.3775 | 0.0126 | 43 | - | - | - |
Age in women | - | - | - | 0.3384 | 0.0305 | 41 |
Age in PD men | −0.4643 | 0.0122 | 29 | - | - | - |
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Arce-López, B.; Alvarez-Erviti, L.; De Santis, B.; Izco, M.; López-Calvo, S.; Marzo-Sola, M.E.; Debegnach, F.; Lizarraga, E.; López de Cerain, A.; González-Peñas, E.; et al. Biomonitoring of Mycotoxins in Plasma of Patients with Alzheimer’s and Parkinson’s Disease. Toxins 2021, 13, 477. https://doi.org/10.3390/toxins13070477
Arce-López B, Alvarez-Erviti L, De Santis B, Izco M, López-Calvo S, Marzo-Sola ME, Debegnach F, Lizarraga E, López de Cerain A, González-Peñas E, et al. Biomonitoring of Mycotoxins in Plasma of Patients with Alzheimer’s and Parkinson’s Disease. Toxins. 2021; 13(7):477. https://doi.org/10.3390/toxins13070477
Chicago/Turabian StyleArce-López, Beatriz, Lydia Alvarez-Erviti, Barbara De Santis, María Izco, Silvia López-Calvo, Maria Eugenia Marzo-Sola, Francesca Debegnach, Elena Lizarraga, Adela López de Cerain, Elena González-Peñas, and et al. 2021. "Biomonitoring of Mycotoxins in Plasma of Patients with Alzheimer’s and Parkinson’s Disease" Toxins 13, no. 7: 477. https://doi.org/10.3390/toxins13070477
APA StyleArce-López, B., Alvarez-Erviti, L., De Santis, B., Izco, M., López-Calvo, S., Marzo-Sola, M. E., Debegnach, F., Lizarraga, E., López de Cerain, A., González-Peñas, E., & Vettorazzi, A. (2021). Biomonitoring of Mycotoxins in Plasma of Patients with Alzheimer’s and Parkinson’s Disease. Toxins, 13(7), 477. https://doi.org/10.3390/toxins13070477