Decreased Blood Level of MFSD2a as a Potential Biomarker of Alzheimer’s Disease
Abstract
:1. Introduction
2. Results
2.1. Demographic Characteristics of Subjects
2.2. Reduced Level of Blood MFSD2a in Alzheimer’s Disease Patients and Impact on Fatty Acid Profile in Serum
2.3. Levels of MFSD2a Expression in Brain Stay Unaltered in Alzheimer’s Disease Patients
3. Discussion
4. Materials and Methods
4.1. Study Population
4.2. Western Blotting Analyses
4.3. Antibodies
4.4. Analysis of Fatty Acids
4.5. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
MFSD2a | Major Facilitator Superfamily Domain containing 2A |
AD | Alzheimer’s disease |
DHA | Docosahexaenoic acid |
EPA | Eicosapentaenoic acid |
GDS | Global Deterioration Scale |
LC-PUFA | Long-chain polyunsaturated fatty acids |
FA | Fatty acid |
BBB | Blood–brain barrier |
CNS | Central nervous system |
GADPH | D-Glyceraldehyde-3-Phosphate Dehydrogenase |
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Control n = 38 | GDS4 n = 48 | GDS6 n = 47 | p | |
---|---|---|---|---|
Sex (n) | 10♂, 28♀ | 13♂, 35♀ | 18♂, 29♀ | 0.385 |
Age | 67 ± 2 | 74 ± 1* | 76 ± 1* | <0.001 |
BMI (kg/m2) | 27.4 ± 0.8 | 26.2 ± 1.8 | 28.9 ± 1.4 | 0.300 |
Hypertension (%) | n/a | 50.0 | 51.1 | 0.917 |
Diabetes (%) | n/a | 27.1 | 26.1 | 0.913 |
Smoking (%) | n/a | 14.6 | 25.5 | 0.182 |
Dementia family history (%) | n/a | 73.9 | 68.3 | 0.563 |
MMSE score | n/a | 18.7 ± 0.7 | 8.3 ± 0.8 † | <0.001 |
Fatty Acid (%) with Respect to Total Fatty Acid Content | Control (n = 38) | GDS4 (n = 48) | GDS6 (n = 45) | p |
---|---|---|---|---|
Lauric acid (12:0) | 0.12 ± 0.03 | 0.12 ± 0.02 | 0.14 ± 0.02 | 0.843 |
Myristic acid (14:0) | 1.49 ± 0.19 | 1.51 ± 0.10 | 1.54 ± 0.15 | 0.971 |
Palmitic acid (16:0) | 21.79 ± 0.30 | 21.74 ± 0.29 | 22.33 ± 0.28 | 0.282 |
Hexadecanoic acid (16:1 n-9) | 0.29 ± 0.01 | 0.31 ± 0.01 | 0.31 ± 0.01 | 0.338 |
Palmitoleic acid (16:1 n-7) | 1.37 ± 0.12 | 1.45 ± 0.09 | 1.63 ± 0.12 | 0.240 |
Margaric acid (17:0) | 0.18 ± 0.02 | 0.22 ± 0.01 | 0.23 ± 0.01* | 0.040 |
Stearic acid (18:0) | 8.39 ± 0.21 | 7.62 ± 0.18* | 7.72 ± 0.18* | 0.012 |
Oleic acid (18:1 n-9) | 20.19 ± 0.63 | 21.10 ± 0.50 | 20.62 ± 0.56 | 0.525 |
Cis-vaccenic acid (18:1 n-7) | 1.59 ± 0.05 | 1.67 ± 0.04 | 1.75 ± 0.06 | 0.073 |
Linoleic acid (18:2 n-6) | 26.64 ± 0.76 | 26.94 ± 0.76 | 26.55 ± 0.77 | 0.931 |
γ-linolenic acid (18:3 n-6) | 0.40 ± 0.03 | 0.42 ± 0.02 | 0.43 ± 0.03 | 0.755 |
α-linolenic acid (18:3 n-3) | 0.16 ± 0.02 | 0.19 ± 0.01 | 0.16 ± 0.01 | 0.319 |
Arachidic acid (20:0) | 0.30 ± 0.02 | 0.31 ± 0.03 | 0.31 ± 0.02 | 0.971 |
Gondoic acid (20:1 n-9) | 0.23 ± 0.03 | 0.29 ± 0.03 | 0.27 ± 0.03 | 0.392 |
Eicosadienoic acid (20:2 n-6) | 0.21 ± 0.03 | 0.40 ± 0.03* | 0.32 ± 0.04* | <0.001 |
Dihomo-γ-linolenic acid (20:3 n-6) | 1.63 ± 0.06 | 1.65 ± 0.05 | 1.59 ± 0.06 | 0.738 |
Arachidonic acid (20:4 n-6, AA) | 7.29 ± 0.29 | 7.20 ± 0.28 | 7.71 ± 0.33 | 0.445 |
Heneicosylic acid (21:0) | 0.05 ± 0.01 | 0.06 ± 0.01 | 0.03 ± 0.01 | 0.073 |
Behenic acid (22:0) | 0.73 ± 0.04 | 0.65 ± 0.03 | 0.63 ± 0.02* | 0.046 |
Adrenic acid (22:4 n-6) | 0.08 ± 0.02 | 0.13 ± 0.02 | 0.12 ± 0.03 | 0.401 |
Docosapentaenoic acid (22:5 n-3) | 0.32 ± 0.02 | 0.28 ± 0.01 | 0.28 ± 0.02 | 0.102 |
Tricosylic acid (23:0) | 0.33 ± 0.02 | 0.26 ± 0.01* | 0.24 ± 0.01* | <0.001 |
Lignoceric acid (24:0) | 0.64 ± 0.04 | 0.58 ± 0.03 | 0.57 ± 0.02 | 0.297 |
Nervonic acid (24:1 n-9) | 0.98 ± 0.06 | 0.94 ± 0.06 | 0.91 ± 0.06 | 0.779 |
SFA | 34.02 ± 0.50 | 33.07 ± 0.43 | 33.74 ± 0.33 | 0.264 |
MUFA | 24.65 ± 0.69 | 25.76 ± 0.55 | 25.50 ± 0.65 | 0.451 |
PUFA | 41.33 ± 0.77 | 41.17 ± 0.73 | 40.76 ± 0.77 | 0.863 |
PUFA n-6 | 36.24 ± 0.79 | 36.74 ± 0.72 | 36.73 ± 0.78 | 0.880 |
PUFA n-3 | 5.09 ± 0.3 | 4.43 ± 0.23 | 4.03 ± 0.23* | 0.018 |
n-6/n-3 | 7.98 ± 0.46 | 9.35 ± 0.50 | 10.23 ± 0.56* | 0.013 |
LC-PUFA n-6 | 9.20 ± 0.31 | 9.39 ± 0.29 | 9.74 ± 0.34 | 0.481 |
LC-PUFA n-3 | 4.92 ± 0.30 | 4.24 ± 0.23 | 3.87 ± 0.23* | 0.017 |
Total Fatty acid concentration (mg/dL) | 384.90 ± 17.11 | 494.31 ± 28.83* | 488.50 ± 34.15* | 0.016 |
Fatty Acid (%) Respect to Total Fatty Acid Content | Control (n = 11) | GDS6 (n = 11) | p |
---|---|---|---|
Lauric acid (12:0) | 0.08 ± 0.02 | 0.05 ± 0.01 | 0.159 |
Palmitic acid (16:0) | 20.00 ± 0.55 | 20.19 ± 1.00 | 0.864 |
Hexadecanoic acid (16:1 n-9) | 0.52 ± 0.03 | 0.59 ± 0.06 | 0.342 |
Palmitoleic acid (16:1 n-7) | 0.65 ± 0.04 | 0.56 ± 0.04 | 0.141 |
Margaric acid (17:0) | 0.30 ± 0.01 | 0.31 ± 0.01 | 0.428 |
Stearic acid (18:0) | 20.55 ± 0.29 | 19.99 ± 0.30 | 0.201 |
Elaidic acid (18:1 trans) | 0.05 ± 0.01 | 0.05 ± 0.01 | 0.911 |
Oleic acid (18:1 n-9) | 17.58 ± 0.68 | 18.44 ± 1.08 | 0.496 |
Cis-vaccenic acid (18:1 n-7) | 4.15 ± 0.21 | 4.37 ± 0.21 | 0.462 |
Linoelaidic acid (18:2 all trans-9,12) | 0.01 ± 0.01 | 0.00 ± 0.00 | 0.374 |
Linoelaidic acid (18:2 trans-12) | 0.03 ± 0.03 | 0.00 ± 0.00 | 0.374 |
Linoleic acid (18:2 n-6) | 0.86 ± 0.09 | 0.76 ± 0.12 | 0.478 |
α-linolenic acid (18:3 n-3) | 0.34 ± 0.04 | 0.34 ± 0.06 | 0.960 |
Arachidic acid (20:0) | 0.27 ± 0.01 | 0.27 ± 0.02 | 0.923 |
Gondoic acid (20:1 n-9) | 0.79 ± 0.10 | 0.89 ± 0.16 | 0.568 |
Eicosadienoic acid (20:2 n-6) | 0.23 ± 0.02 | 0.29 ± 0.02 | 0.075 |
Dihomo-γ-linolenic acid (20:3 n-6) | 1.08 ± 0.07 | 1.03 ± 0.08 | 0.623 |
Eicosatrienoic acid (20:3 n-3) | 0.02 ± 0.02 | 0.00 ± 0.00 | 0.374 |
Arachidonic acid (20:4 n-6, AA) | 8.83 ± 0.35 | 8.60 ± 0.48 | 0.697 |
Eicosapentaenoic acid (20:5 n-3, EPA) | 0.05 ± 0.04 | 0.00 ± 0.00 | 0.174 |
Behenic acid (22:0) | 0.48 ± 0.08 | 0.65 ± 0.08 | 0.159 |
Erucic acid (22:1 n-9) | 0.05 ± 0.01 | 0.09 ± 0.01 | 0.073 |
Adrenic acid (22:4 n-6) | 4.78 ± 0.14 | 4.32 ± 0.17 | 0.051 |
Docosapentaenoic acid (22:5 n-6, DPA) | 1.23 ± 0.10 | 1.89 ± 0.23* | 0.022 |
Docosapentaenoic acid (22:5 n-3) | 0.41 ± 0.07 | 0.26 ± 0.03 | 0.079 |
Docosahexaenoic acid (22:6 n-3, DHA) | 11.83 ± 0.80 | 10.77 ± 1.20 | 0.458 |
Tricosylic acid (23:0) | 0.14 ± 0.07 | 0.10 ± 0.06 | 0.679 |
Lignoceric acid (24:0) | 1.05 ± 0.16 | 1.20 ± 0.29 | 0.653 |
Nervonic acid (24:1 n-9) | 3.63 ± 0.53 | 4.00 ± 0.98 | 0.734 |
SFA | 42.88 ± 0.47 | 42.77 ± 0.79 | 0.903 |
MUFA | 27.37 ± 1.32 | 28.93 ± 2.12 | 0.525 |
PUFA | 29.67 ± 0.94 | 28.26 ± 1.41 | 0.402 |
TRANS | 0.09 ± 0.04 | 0.05 ± 0.01 | 0.349 |
PUFA n-6 | 17.02 ± 0.37 | 16.89 ± 0.51 | 0.832 |
PUFA n-3 | 12.65 ± 0.78 | 11.37 ± 1.14 | 0.355 |
n-6/n-3 | 1.44 ± 0.15 | 1.69 ± 0.27 | 0.410 |
LC-PUFA n-6 | 16.16 ± 0.33 | 16.13 ± 0.53 | 0.966 |
LC-PUFA n-3 | 12.31 ± 0.82 | 11.03 ± 1.19 | 0.374 |
Total Fatty Acid concentration (mg/g) | 23.82 ± 1.09 | 22.37 ± 1.62 | 0.454 |
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Sánchez-Campillo, M.; Ruiz-Pastor, M.J.; Gázquez, A.; Marín-Muñoz, J.; Noguera-Perea, F.; Ruiz-Alcaraz, A.J.; Manzanares-Sánchez, S.; Antúnez, C.; Larqué, E. Decreased Blood Level of MFSD2a as a Potential Biomarker of Alzheimer’s Disease. Int. J. Mol. Sci. 2020, 21, 70. https://doi.org/10.3390/ijms21010070
Sánchez-Campillo M, Ruiz-Pastor MJ, Gázquez A, Marín-Muñoz J, Noguera-Perea F, Ruiz-Alcaraz AJ, Manzanares-Sánchez S, Antúnez C, Larqué E. Decreased Blood Level of MFSD2a as a Potential Biomarker of Alzheimer’s Disease. International Journal of Molecular Sciences. 2020; 21(1):70. https://doi.org/10.3390/ijms21010070
Chicago/Turabian StyleSánchez-Campillo, María, María José Ruiz-Pastor, Antonio Gázquez, Juan Marín-Muñoz, Fuensanta Noguera-Perea, Antonio J. Ruiz-Alcaraz, Salvadora Manzanares-Sánchez, Carmen Antúnez, and Elvira Larqué. 2020. "Decreased Blood Level of MFSD2a as a Potential Biomarker of Alzheimer’s Disease" International Journal of Molecular Sciences 21, no. 1: 70. https://doi.org/10.3390/ijms21010070