Plasma Neurofilament Light Chains as Blood-Based Biomarkers for Early Diagnosis of Canine Cognitive Dysfunction Syndrome
Abstract
:1. Introduction
2. Results
2.1. Canine CCDR Scores
2.2. Canine Plasma NfL Levels
2.3. Canine Blood Test
3. Discussion
4. Materials and Methods
4.1. Sampling Population
4.2. Behavioral Scoring for Cognitive Impairment
4.3. Screening NfL Using IMR Assay
4.4. Clinical Observations and Blood Tests
4.5. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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ND (N = 21) | CCD (N = 15) | |||
---|---|---|---|---|
Sex (number) | M: 10 (48%) | F: 11 (52%) | M: 7 (47%) | F: 8 (53%) |
Age (years) (Range) | 7.32 ± 3.16 (3–16) | 7.68 ± 3.64 (3–14) | 14.37 ± 3.03 ** (12–17) | 13.87 ± 3.22 ** (10–17) |
Body weight (kg) (Range) | 4.2 ± 2.2 (2.1–7.2) | 4.5 ± 1.2 (2.3–7.5) | 5.2 ± 2.7 (3.3–8.6) | 4.9 ± 2.5 (2.8–8.4) |
NfL levels (pg/mL) (Range) | 7.97 ± 1.36 (5.77–10.37) | 8.02 ± 1.63 (6.14–10.67) | 9.37 ± 1.70 ** (7.63–13.03) | 9.92 ± 1.05 ** (8.03–11.40) |
Biochemical Parameters | ND (N = 21) | CCD (N = 15) |
---|---|---|
Hematocrit (%) | 42.49 ± 7.23 | 39.83 ± 7.67 |
Hemoglobin (g/dL) | 14.66 ± 2.64 | 13.60 ± 2.48 |
WBC (K/µL) | 10.11 ± 2.19 | 10.18 ± 2.52 |
White blood cell count (K/µL) | 6.36 ± 3.22 | 7.27 ± 3.74 |
Eosinophil count (K/µL) | 1.21 ± 0.85 | 1.22 ± 0.73 |
Granules count (K/µL) | 7.64 ± 2.09 | 7.38 ± 2.12 |
Platelet count (K/µL) | 310.53 ± 83.61 | 313.58 ± 87.66 |
Glucose concentration (mg/dL) | 94.68 ± 13.19 | 96.69 ± 13.13 |
Symmetric dimethylarginine (µg/dL) | 9.24 ± 3.12 | 13.17 ± 3.23 * |
Creatinine (mg/dL) | 1.27 ± 0.32 | 1.98 ± 0.28 * |
Urea nitrogen (mg/dL) | 23.13 ± 8.16 * | 29.75 ± 831 * |
Total protein (g/dL) | 60.27 ± 4.26 | 69.89 ± 4.22 * |
Albumins (g/dL) | 32.86 ± 3.32 | 41.78 ± 3.95 * |
Globulins (g/dL) | 3.83 ± 1.15 | 3.93 ± 1.21 |
Aspartate transaminase (AST/GOT) (U/L) | 40.26 ± 3.72 | 48.57 ± 3.52 * |
Alanine transaminase (ALT/GPT) (U/L) | 53.89 ± 7.11 | 108.21 ± 6.79 ** |
Alkaline Phosphatase (ALP) (U/L) | 86.45 ± 7.98 | 106.50 ± 9.12 ** |
Glutamyl transferase (GMT) (U/L) | 9.53 ± 0.66 | 16.67 ± 0.72 ** |
Bilirubin (mg/dL) | 0.21 ± 0.15 | 0.23 ± 0.15 |
Cholesterol (mg/dL) | 198.22 ± 25.2 | 237.42 ± 26.3 * |
C-reactive protein (CRP) (mg/dL) | 0.65 ± 0.17 | 2.39 ± 0.17 ** |
Phosphorus (mg/dL) | 3.90 ± 1.09 | 3.74 ± 1.04 |
Calcium (mg/dL) | 9.76 ± 0.45 | 9.95 ± 0.47 |
Sodium concentration (mmol/L) | 138.00 ± 2.29 | 113.58 ± 2.45 * |
Potassium concentration (mmol/L) | 4.51 ± 1.78 | 4.44 ± 1.69 |
Chloride concentration (mmol/L) | 115.33 ± 6.42 | 93.25 ± 6.67 * |
Assay Platform | Limits of Detection | Refs. |
---|---|---|
ELISA | 5–250 pg/mL | [16,17,18] |
SIMOA | 0.97–2.2 pg/mL | [19,20] |
ECL | 15.6 pg/ml | [21] |
IMR | 0.18 fg/mL | [15] |
DOMAINS/ITEMS |
---|
A. SPATIAL ORIENTATION [SCORE (0–25)] |
1. disorientation in a familiar environment (inside/outside) |
2. recognition familiar people and animals inside or outside the house/apartment |
3. abnormally respond to familiar object (a chair, a wastebasket) |
4. aimlessly wandering (motorically restless during day) |
5. reduced ability to do previously learned tasks |
B. SOCIAL INTERACTION [SCORE (0–25)] |
1. changes in interaction a man/dog, dog/other dog (playing, petting, welcoming) |
2. changes in individual behavior of dog (exploration behavior, play, performance) |
3. response to commands and ability to learn new tasks |
4. irritability |
5. expression of aggression |
C. SLEEP-WAKE CYCLES [SCOREx2 (0–20)] |
1. abnormally responds in night (wandering, vocalization, motirically restless) |
2. switch over from insomnia to hypersomnia |
D. HOUSE SOILING [SCORE (0–25)] |
1. eliminate at home at random locations |
2. eliminate in its kennel or sleeping area |
3. changes in signalization for elimination activity |
4. eliminate indoors after a recent walk outside |
5. eliminate at uncommon locations (grass, concentrate) |
TOTAL SCORE (A+B+C+D) (0–95) |
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Wu, C.-H.; Pan, X.-S.; Su, L.-Y.; Yang, S.-Y. Plasma Neurofilament Light Chains as Blood-Based Biomarkers for Early Diagnosis of Canine Cognitive Dysfunction Syndrome. Int. J. Mol. Sci. 2023, 24, 13771. https://doi.org/10.3390/ijms241813771
Wu C-H, Pan X-S, Su L-Y, Yang S-Y. Plasma Neurofilament Light Chains as Blood-Based Biomarkers for Early Diagnosis of Canine Cognitive Dysfunction Syndrome. International Journal of Molecular Sciences. 2023; 24(18):13771. https://doi.org/10.3390/ijms241813771
Chicago/Turabian StyleWu, Chung-Hsin, Xun-Sheng Pan, Li-Yu Su, and Shieh-Yueh Yang. 2023. "Plasma Neurofilament Light Chains as Blood-Based Biomarkers for Early Diagnosis of Canine Cognitive Dysfunction Syndrome" International Journal of Molecular Sciences 24, no. 18: 13771. https://doi.org/10.3390/ijms241813771