Personalized Management and Treatment of Alzheimer’s Disease
Abstract
:1. Introduction
2. Diagnostic Procedures
3. Phenotypic Features
4. Biomarkers
4.1. Genomic Markers
4.2. Epigenetic Markers
4.3. Neurotransmitters
4.4. Aβ/Tau Levels
5. Concomitant Disorders and Phenotype-Modifying Treatments
6. Alzheimer’s Disease Therapeutics and Drug Development
Immunotherapy
7. Pharmacogenomics
7.1. The Pharmacogenomic Machinery in Alzheimer’s Disease
7.2. Mechanistic Genes Involved in Cholinergic Neurotransmission
7.3. Metabolic Genes
7.4. Transporter Genes
7.5. Pharmacogenetics of Acetylcholinesterase Inhibitors
7.5.1. Donepezil
7.5.2. Galantamine
7.5.3. Rivastigmine
7.5.4. Huperzine A
7.6. Pharmacogenetics of Memantine
7.7. Pharmacogenetics of Aducanumab
7.8. Pharmacogenetics of Multifactorial Treatments
7.9. Pharmacoepigenetics
7.10. Pharmacogenomics of Mood Disorders and Anxiety
8. Future Trends
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Parameter (Normal Range) | Total | Females | Males | Differences |
---|---|---|---|---|
N | 2701 | 1491 (55%) | 1210 (45%) | |
Age (years) Range | 67.63 ± 0.19 50–96 | 68.26 ± 0.27 50–96 | 66.86 ± 0.28 50–94 | p < 0.001 |
Systolic blood pressure (mm Hg) (120–160) | 141.39 ± 0.41 <120: 13.74% >160: 21.84% | 141.25 ± 0.56 14.75% 22.25% | 141.56 ± 0.61 12.37% 21.33% | p = 0.74 p(χ2) = 0.13 p(χ2) = 0.66 |
Diastolic blood pressure (mm Hg) (70–85) | 79.38 ± 0.21 <70: 10.48% >85: 28.53% | 78.83 ± 0.28 11.27% 26.84% | 80.05 ± 0.33 9.54% 30.74% | p < 0.001 p(χ2) = 0.24 p(χ2) = 0.10 |
Pulse (bpm) (60–100) | 68.29 ± 0.23 <60: 23.34% >100: 2.07% | 69.60 ± 0.31 19.05% 2.35% | 66.67 ± 0.35 28.75% 1.74% | p < 0.001 p(χ2) = 0.003 p(χ2) = 0.34 |
Weight (Kg) | 72.23 ± 0.27 (36–127) | 66.41 ± 0.32 (36–112) | 79.41 ± 0.37 (42–127) | p < 0.001 |
Hight (cm) | 160.71 ± 0.21 (120–188) | 154.96 ± 0.21 (140–182) | 167.79 ± 0.26 (120–188) | p < 0.001 |
BMI (Kg/m2) Underweight (15–18.5) Normal weight (18.5–25) Overweight (25–30) Obese Class I (moderate) (30–35) Obese Class II (severe)(35–40) Obese Class III (very severe) (>40) | 29.93 ± 0.09 1.01% 25.03% 45.26% 21.25% 6.08% 1.33% | 27.76 ± 0.13 1.54% 29.15% 39.50% 20.85% 7.34% 1.62% | 28.15 ± 0.11 0.27% 19.86% 52.35% 21.75% 4.69% 1.08% | p < 0.002 p(χ2) < 0.003 p(χ2) < 0.001 p(χ2) < 0.001 p(χ2) = 0.69 p(χ2) < 0.01 p(χ2) = 0.34 |
Glucose (mg/dL) (70–105) | 102.00 ± 0.55 <70: 0.41% >105: 26.55% | 99.17 ± 0.69 0.54% 21.63% | 105.49 ± 0.87 0.24% 32.70% | p < 0.001 p(χ2) = 0.38 p(χ2) < 0.001 |
Cholesterol (mg/dL) (140–220) | 219.02 ± 0.90 <140: 3.60% >220: 40.54% | 228.61 ± 1.22 1.81% 56.27% | 207.20 ± 1.28 5.79% 21.16% | p < 0.001 p(χ2) < 0.001 p(χ2) < 0.001 |
HDL-cholesterol (mg/dL) (35–75) | 55.04 ± 0.28 <35: 5.37% >75: 10.11% | 59.98 ± 0.38 2.35% 15.49% | 48.95 ± 0.34 9.09% 3.47% | p < 0.001 p(χ2) < 0.001 p(χ2) < 0.001 |
LDL-cholesterol (mg/dL) (80–160) | 140.85 ± 0.77 <80: 5.15% >160: 29.54% | 146.08 ± 1.03 3.69% 33.67% | 134.41 ± 1.12 6.94% 24.46% | p < 0.001 p(χ2) < 0.001 p(χ2) < 0.001 |
Triglycerides (mg/dL) (50–150) | 113.83 ± 1.31 <50: 5.59% >150: 19.44% | 108.47 ± 1.50 5.97% 16.63% | 120.44 ± 2.26 5.12% 22.89% | p < 0.001 p(χ2) = 0.41 p(χ2) < 0.001 |
Urea (mg/dL) (15–30) | 42.90 ± 0.26 <15: 0.34% >30: 88.49% | 41.79 ± 0.33 0.34% 86.45% | 44.27 ± 0.40 0.34% 90.99% | p < 0.001 p = 0.75 p(χ2) = 0.37 |
Creatinine (mg/dL) (0.70–1.40) | 0.91 ± 0.006 <0.70: 14.03% >1.40: 3.59% | 0.81 ± 0.004 23.47% 1.74% | 1.03 ± 0.01 2.40% 8.26% | p < 0.001 p(χ2) < 0.001 p(χ2) < 0.001 |
Uric acid (mg/dL) (3.4–7.0) | 4.47 ± 0.03 <3.4: 23.77% >7.0: 6.03% | 3.90 ± 0.03 36.02% 2.48% | 5.17 ± 0.05 8.68% 10.41% | p < 0.001 p(χ2) < 0.001 p(χ2) < 0.001 |
Total Protein (g/dL) (6.5–8.0) | 6.93 ± 0.03 <6.5: 13.77% >8.0: 1.78% | 6.90 ± 0.01 12.54% 1.61% | 6.97 ± 0.07 15.29% 1.98% | p = 0.17 p(χ2) = 0.08 p(χ2) = 0.56 |
Albumin (g/dL) (3.5–5.0) | 4.20 ± 0.007 <3.5: 1.40% >5.0: 0.95% | 4.18 ± 0.008 1.50% 0.58% | 4.21 ± 0.01 1.60% 1.60% | p = 0.02 p(χ2) = 0.99 p(χ2) = 0.03 |
Calcium (mg/dL) (8.1–10.4) | 9.24 ± 0.009 <8.1: 0.41% >10.4: 2.04% | 9.27 ± 0.01 0.20% 2.35% | 9.19 ± 0.01 0.66% 1.65% | p < 0.001 p(χ2) = 0.12 p(χ2) = 0.26 |
Phosphorus (mg/dL) (2.5–5.0) | 3.41 ± 0.01 <2.5: 2.41% >5.0: 0.67% | 3.52 ± 0.01 0.92% 0.81% | 3.27 ± 0.01 3.47% 0.49% | p < 0.001 p(χ2) < 0.002 p(χ2) = 0.46 |
GOT/ASAT (IU/L) (10–40) | 21.70 ± 0.20 <10: 0.45% >40: 3.85% | 21.29 ± 0.42 0.60% 3.35% | 22.20 ± 0.39 0.25% 4.46% | p = 0.006 p(χ2) = 0.83 p(χ2) = 0.18 |
GPT/ALAT (IU/L) (9–43) | 23.52 ± 0.36 <9: 2.81% >43: 7.07% | 21.51 ± 0.45 3.02% 4.96% | 26.00 ± 0.56 2.56% 9.67% | p < 0.001 p(χ2) = 0.56 p(χ2) < 0.001 |
GGT (IU/L) (11–50) | 30.55 ± 0.79 <11: 7.55% >50: 11.81% | 26.37 ± 1.07 11.54% 8.52% | 35.69 ± 1.17 2.65% 15.87% | p < 0.001 p(χ2) < 0.001 p(χ2) < 0.001 |
Alkaline phosphatase (IU/L) (37–111) | 77.05 ± 0.62 <37: 2.07% >111: 10.37% | 79.41 ± 0.85 1.74% 10.39% | 74.14 ± 0.82 2.48% 10.83% | p < 0.001 p(χ2) = 0.24 p(χ2) = 0.98 |
Bilirubin (mg/dL) (0.20–1.00) | 0.75 ± 0.02 <0.20: 0.30% >1.00: 15.07% | 0.71 ± 0.04 0.34% 10.33% | 0.80 ± 0.01 0.24% 20.91% | p < 0.001 p(χ2) = 0.95 p(χ2) < 0.001 |
CPK (IU/L) (38–174) | 92.72 ± 2.00 <38: 8.22% >174: 7.29% | 87.20 ± 3.12 9.25% 5.03% | 99.52 ± 2.29 6.94% 10.08% | p < 0.001 p(χ2) < 0.05 p(χ2) < 0.001 |
LDH (IU/L) (200–480) | 277.29 ± 1.52 <200: 13.59% >480: 1.74% | 289.77 ± 2.06 6.71% 2.21% | 261.88 ± 2.16 15.87% 1.16% | p < 0.001 p(χ2) < 0.008 p(χ2) < 0.05 |
Na+ (mEq/L) (135–148) | 141.75 ± 0.04 <135: 0.70% >148: 0.89% | 141.86 ± 0.05 0.36% 0.80% | 141.62 ± 0.06 0.82% 0.99% | p < 0.002 p(χ2) = 0.65 p(χ2) = 0.76 |
K+ (mEq/L) (3.5–5.3) | 4.33 ± 0.006 <3.5: 0.85% >5.3: 1.15% | 4.29 ± 0.009 1.07% 0.67% | 4.38 ± 0.009 0.57% 1.74% | p < 0.001 p(χ2) = 0.24 p(χ2) < 0.01 |
Cl- (mEq/L) (98–107) | 104.06 ± 0.07 <98: 1.22% >107: 13.92% | 104.20 ± 0.13 1.07% 14.89% | 103.88 ± 0.07 1.40% 12.96% | p < 0.04 p(χ2) = 0.55 p(χ2) = 0.29 |
Fe2+ (µg/dL) (35–160) | 86.60 ± 0.70 <35: 5.04% >160: 2.61% | 81.98 ± 0.89 7.01% 1.64% | 92.17 ± 1.10 3.80% 4.20% | p < 0.001 p(χ2) < 0.01 p(χ2) < 0.001 |
Ferritin (ng/mL) (F: 11–307) (M: 24–336) | 121.05 ± 2.91 <11: 3.43% >307: 7.65% | 81.01 ± 2.48 <11: 5.55% >307: 2.09% | 169.39 ± 5.32 <24: 1.8% >336: 15.3% | p < 0.001 p(χ2) < 0.001 p(χ2) < 0.001 |
Folate (ng/mL) (>3.00) | 7.94 ± 0.08 <5: 27.14% | 8.31 ± 0.12 23.27% | 7.48 ± 0.12 31.90% | p < 0.001 p(χ2) < 0.001 |
Vitamin B12 (pg/mL) (170–1000) | 481.98 ± 5.37 <200: 10.10% | 499.87 ± 7.60 6.71% | 459.99 ± 7.44 14.30% | p < 0.001 p(χ2) < 0.001 |
TSH (µIU/mL) (0.20–4.50) | 1.54 ± 0.04 <0.20: 2.55% >4.50: 2.37% | 1.67 ± 0.07 3.02% 2.88% | 1.38 ± 0.03 1.98% 1.73% | p < 0.001 p(χ2) = 0.12 p(χ2) = 0.07 |
T4 (ng/mL) (0.54–1.40) | 0.94 ± 0.01 <0.54: 0.77% >1.40: 3.15% | 0.94 ± 0.02 1.07% 3.15% | 0.94 ± 0.01 0.41% 3.14% | p = 0.55 p(χ2) = 0.08 p(χ2) = 0.92 |
PRL (ng/mL) (F: 1.9–25) (M: 2.5–17) | 10.18 ± 0.53 <1.9: 3.48% >25: 6.53% | 11.74 ± 0.89 <1.9: 2.08% >25: 6.69% | 8.19 ± 0.41 <2.5: 5.17% >17: 6.32% | p < 0.001 p(χ2) < 0.03 p(χ2) = 0.95 |
Cortisol (µg/dL) (6.02–18.4) | 13.46 ± 0.18 <6: 10% >18: 26.25% | 13.31 ± 0.24 4.39% 17.32% | 13.64 ± 0.26 3.74% 15.80% | p = 0.30 p(χ2) = 0.79 p(χ2) = 0.70 |
ACTH (pg/mL) (<46) | 23.31 ± 0.62 >50: 5.25% | 21.11 ± 0.78 3.69% | 26.10 ± 0.99 7.18% | p < 0.001 p(χ2) < 0.05 |
GH (ng/mL) (F. 0.12–9.88) (M: 0.03–2.47) | 0.76 ± 0.04 <0.03–0.12: 11.14% >2.47–9.80: 4.26% | 0.77 ± 0.06 >0.12: 18.25% >9.80: 0.46% | 0.75 ± 0.06 <0.03: 2.3% >2.47: 8.91% | p < 0.04 p(χ2) < 0.001 p(χ2) < 0.001 |
FSH (mIU/mL) (F: 21.7–153) (M: 0.7–11.1) | 41.37 ± 1.36 <0.7–21.7: 4.10% >11–1–153: 11.14% | 67.07 ± 1.57 <21: 6.93% >153: 0.92% | 9.39 ± 0.47 <0.7: 0.57% >11: 23.85% | p < 0.001 p(χ2) < 0.001 p(χ2) < 0.001 |
LH (mIU/mL) (F: 7.7–58.5) (M: 1.7–8.6) | 16.84 ± 0.53 <1.7–7.7: 6.79% >8.6–58.5: 7.30% | 26.04 ± 0.63 <7.7: 7.16% >58.5: 2.77% | 5.38 ± 0.20 <1.7: 6.32% >8.6: 12.93% | p < 0.001 p(χ2) = 0.77 p(χ2) < 0.001 |
Estrogen (pg/mL) (20–30) | 26.23 ± 1.29 <20: 6.95% >30: 16.31% | |||
Testosterone (ng/dL) (193–740) | 281.45 ± 11.49 <190: 31.15% >740: 1.87% | |||
α-Amylase (U/L) (28–100) | 59.98 ± 1.26 >100: 6.70% | 57.94 ± 1.64 5.70% | 62.67 ± 1.95 7.77% | p = 0.05 p(χ2) = 0.43 |
Lipase (U/L) (13–60) | 43.62 ± 0.71 >60: 10.58% | 42.98 ± 0.76 9.56% | 44.46 ± 1.29 11.94% | p = 0.75 p(χ2) = 0.42 |
AFP (ng/mL) (0–7) | 3.17 ± 0.10 >7: 5.44% | 3.33 ± 0.10 5.88% | 2.97 ± 0.19 4.85% | p < 0.001 p(χ2) = 0.68 |
CEA (ng/mL) (0–3.8) | 3.97 ± 1.40 >3.8: 16.76% | 2.32 ± 0.09 12.99% | 6.14 ± 2.26 21.75% | p < 0.05 p(χ2) < 0.01 |
CA 19.9 (U/mL) (0–27) | 14.41 ± 2.05 >27: 8.94% | 11.60 ± 0.61 7.35% | 18.14 ± 4.70 11.04% | p = 0.27 p(χ2) = 0.15 |
CA 72.4 (U/mL) (0–6.9) | 3.96 ± 0.86 >6.9: 13.01% | 4.86 ± 1.46 14.71% | 2.85 ± 0.66 10.91% | p = 0.18 p(χ2) = 0.78 |
CA 125 (U/mL) (0–35) | 16.38 ± 1.67 >35: 5.97% | 15.82 ± 2.42 4.19% | 17.16 ± 2.14 8.50% | p = 0.87 p(χ2) = 0.16 |
CYFRA 21.1 (ng/mL) (0–3.3) | 1.85 ± 0.08 >3.3: 10.39% | 1.76 ± 0.06 9.52% | 1.94 ± 0.15 11.32% | p = 0.83 p(χ2) = 0.76 |
SCC (ng/mL) (0–2.3) | 1.30 ± 0.09 >2.3: 9.785 | 1.05 ± 0.05 6.59% | 1.55 ± 0.18 12.96% | p < 0.001 p(χ2) = 0.11 |
NSE (ng/mL) (0–16.3) | 10.28 ± 0.17 >16.3: 3.95% | 10.77 ± 0.24 5.36% | 9.78 ± 0.23 2.48% | p < 0.001 p(χ2) = 0.31 |
PSA (ng/mL) (<4) | 2.31 ± 0.16 >4: 13.45% | |||
CA 15.3 (U/mL) (0–26.4) | 14.05 ± 0.58 >26.4: 7.25% | |||
RBC (×106/µL) (3.80–5.50) | 4.62 ± 0.008 <3.80: 2.78% >5.50: 3.99% | 4.47 ± 0.01 4.09% 2.01% | 4.81 ± 0.01 1.16% 6.45% | p < 0.001 p(χ2) < 0.001 p(χ2) = 0.001 |
HCT (%) (40.0–50.0) | 42.41 ± 0.23 <40.0: 29.58% >50.0: 3.07% | 40.69 ± 0.26 42.85% 0.54% | 44.53 ± 0.39 13.22% 6.19% | p < 0.001 p(χ2) = 0.001 p(χ2) = 0.001 |
Hb (g/dL) (13.5–17.0) | 14.04 ± 0.02 <13.5: 32.06% >17.0: 2.29% | 13.47 ± 0.03 46.88% 0.13% | 14.74 ± 0.04 13.80% 4.95% | p < 0.001 p(χ2) = 0.001 p(χ2) = 0.001 |
MCV (fL) (80–100) | 91.06 ± 0.10 <80: 2.29% >100: 3.59% | 90.48 ± 0.13 2.41% 2.55% | 91.77 ± 0.15 2.15% 4.88% | p < 0.001 p(χ2) = 0.75 p(χ2) < 0.003 |
MCH (pg) (27.0–33.0) | 30.41 ± 0.03 <27.0: 3.62% >33.0: 5.48% | 30.19 ± 0.05 4.02% 5.23% | 30.69 ± 0.05 3.14% 8.26% | p < 0.001 p(χ2) = 0.28 p(χ2) < 0.004 |
MCHC (g/dL) (31.0–35.0) | 33.37 ± 0.01 <31.0: 0.63% >35.0: 2.33% | 33.32 ± 0.02 0.80% 2.35% | 33.43 ± 0.02 0.41% 2.31% | p < 0.002 p(χ2) = 0.30 p(χ2) = 0.94 |
ADE (RDW) (%) (11.0–15.0) | 12.95 ± 0.02 <11.0: 1.81% >15.0: 5.63% | 13.01 ± 0.03 1.61% 6.24% | 12.88 ± 0.03 2.07% 4.88% | p < 0.05 p(χ2) = 0.47 p(χ2) = 0.17 |
WBC (×103/µL) (4.0–11.0) | 6.35 ± 0.03 <4.0: 5.41% >11.0: 2.55% | 6.18 ± 0.05 7.18% 2.28% | 6.56 ± 0.05 3.47% 2.89% | p < 0.001 p(χ2) < 0.001 p(χ2) = 0.39 |
%Neu (45.0–70.0) | 60.15 ± 0.19 <45.0: 6.03% >70.0: 17.92% | 59.98 ± 0.25 7.04% 15.16% | 60.35 ± 0.30 4.79% 16.86% | p = 0.22 p(χ2) < 0.02 p(χ2) = 0.33 |
%Lym (20.0–40.0) | 29.60 ± 0.22 <20: 13.44% >40: 11.51% | 30.22 ± 0.22 11.80% 12.81% | 28.83 ± 0.42 15.45% 9.92% | p < 0.001 p(χ2) < 0.02 p(χ2) < 0.04 |
%Mon (3.0–10.0) | 7.24 ± 0.03 <3.0: 1.33% >10.0: 9.48% | 7.03 ± 0.05 1.67% 7.31% | 7.50 ± 0.06 0.91% 12.15% | p < 0.001 p(χ2) = 0.12 p(χ2) < 0.001 |
%Eos (1.0–5.0) | 2.81 ± 0.05 <1.0: 5.73% >5.0: 23.92% | 2.61 ± 0.06 6.71% 24.21% | 3.05 ± 0.09 4.55% 23.55% | p < 0.001 p(χ2) < 0.001 p(χ2) < 0.001 |
%Bas (0.0–1.0) | 0.69 ± 0.07 >1.0: 14.09% | 0.69 ± 0.14 9.09% | 0.69 ± 0.01 19.60% | p < 0.001 p(χ2) < 0.001 |
PLT (×103/µL) (150–450) | 227.11 ± 1.25 <150: 7.59% >450: 0.66% | 239.85 ± 1.67 4.63% 0.55% | 211.29 ± 1.80 11.24% 0.85% | p < 0.001 p(χ2) < 0.001 p(χ2) = 0.49 |
MPV (fL) (6.0–10.0) | 8.55 ± 0.01 <6.0: 0.18% >10.0: 9.03% | 8.55 ± 0.02 0.13% 8.58% | 8.55 ± 0.02 0.25% 9.58% | p = 0.99 p(χ2) = 0.49 p(χ2) = 0.44 |
MMSE Score (0–30) <25/30 | 23.05 ± 0.13 47.38% | 22.07 ± 0.19 54.46% | 24.25 ± 0.19 38.68% | p < 0.001 p(χ2) < 0.001 |
ADAS-Cog | 9.37 ± 0.21 | 9.94 ± 0.30 | 8.65 ± 0.31 | p < 0.001 |
ADAS-Mem | 11.40 ± 0.12 | 11.67 ± 0.16 | 11.05 ± 0.17 | p < 0.02 |
ADAS-Cog-T | 19.06 ± 0.30 | 19.91 ± 0.41 | 18.04 ± 0.43 | p < 0.002 |
ADAS-NonCog | 4.75 ± 0.08 | 5.36 ± 0.12 | 3.98 ± 0.12 | p < 0.001 |
ADAS-T | 23.18 ± 0.36 | 24.66 ± 0.49 | 21.34 ± 0.51 | p < 0.001 |
HARS <10: Normal 11–17: Mild 18–24: Mild-Moderate 25–30: Moderate-Severe | 11.28 ± 0.11 39.97% 46.65% 11.36% 2.01% | 12.45 ± 0.15 30.73% 51.29% 15.04% 2.94% | 9.82 ± 0.15 51.37% 40.94% 6.81% 0.88% | p < 0.001 p < 0.001 p < 0.002 p < 0.001 p < 0.001 |
HDRS 0–7: Normal 8–13: Mild 14–18: Moderate 19–22: Severe >23: Very Severe | 10.06 ± 0.10 34.60% 41.03% 17.18% 4.78% 2.41% | 11.02 ± 0.14 28.67% 42.65% 21.84% 6.54% 3.24% | 8.88 ± 0.15 42.93% 40.55% 12.19% 2.83% 1.50% | p < 0.001 p < 0.001 p = 0.52 p < 0.001 p < 0.001 p < 0.01 |
ECG Normal Borderline Abnormal | 48.44% 10.73% 40.83% | 52.10% 9.12% 38.78% | 43.89% 12.74% 43.37% | p < 0.01 p < 0.01 p = 0.13 |
MRI Normal Abnormal | 26.78% 73.22% | 29.00% 71.00% | 24.16% 75.84% | p = 0.52 p = 0.20 |
Gene | Gene Name | OMIM | Location | dbSNP | Polymorphism | MAF | Genotype |
---|---|---|---|---|---|---|---|
AA: 45.61% | |||||||
A2M | alpha-2-macroglobulin | 103,950 | chr12:9067708 | rs669 | c.2998A>G | 0.31 (G) | AG: 40.35% |
GG: 14.04% | |||||||
TT: 77.19% | |||||||
ABCA7 | ATP binding cassette subfamily A member 7 | 605,414 | chr19:1046521 | rs3764650 | c.1622+115T>G | 0.20 (G) | TG: 21.05% |
GG: 1.76% | |||||||
CC: 21.05% | |||||||
ACE | angiotensin I converting enzyme | 106,180 | chr17:63477060 | rs4332 | c.496-66T>C | 0.47 (T) | CT: 54.39% |
TT: 24.56% | |||||||
*2*2: <1% | |||||||
*2*3: 1.75% | |||||||
APOE | apolipoprotein E | 107,741 | chr19:44908822 | rs7412 | c.4070C>T | 0.08 (T) | *2*4: 1.75% |
rs429358 | c.3932T>C | 0.15 (C) | *3*3: 59.65% | ||||
*3*4: 33.34% | |||||||
*4*4: 3.51% | |||||||
AA: 42.11% | |||||||
BIN1 | bridging integrator 1 | 601,248 | chr2:127137039 | rs744373 | g.127137039A>G | 0.36 (G) | AG: 50.88% |
GG: 7.01% | |||||||
CC: 59.65% | |||||||
C9ORF72 | chromosome 9 open reading frame 72 | 614,260 | chr9:27543280 | rs3849942 | g.27543283T>C | 0.22 (T) | TC: 36.84% |
TT: 3.51% | |||||||
GG: 36.84% | |||||||
CLU | Clusterin | 185,430 | chr8:27607002 | rs11136000 | c.247-478A>G | 0.38 (A) | AG: 49.12% |
AA: 14.04% | |||||||
CC: 17.54% | |||||||
CPZ | carboxypeptidase Z | 603,105 | chr4:8650823 | rs7436874 | g.8649098C>T | 0.36 (C) | CT: 47.37% |
TT: 35.09% | |||||||
GG: 64.92% | |||||||
CR1 | complement C3b/C4b receptor 1 | 120,620 | chr1:207611623 | rs3818361 | c.4946-54A>G | 0.25 (A) | AG: 29.82% |
AA: 5.26% | |||||||
TT: 94.74% | |||||||
DISC1 | disrupted in schizophrenia 1 | 605,210 | chr1:232155150 | rs16856202 | c.2242-7030T>G | 0.03 (G) | TG: 5.26% |
GG: <1% | |||||||
AA: 45.61% | |||||||
LHFPL6 | LHFPL tetraspan subfamily member 6 | 606,710 | chr13:39872236 | rs7995844 | g.39298100G>A | 0.35 (G) | GA: 38.60% |
GG: 15.79% | |||||||
CC: 49.12% | |||||||
MS4A4E | membrane spanning 4-domains A4E | 608,401 | chr11:60204322 | rs670139 | c.279-2443C>A | 0.38 (A) | CA: 42.11% |
AA: 8.77% | |||||||
CC: 36.84% | |||||||
MS4A6A | membrane spanning 4-domains A6A | 606,548 | chr11:60171834 | rs610932 | c.*149+175A>C | 0.45 (A) | CA: 38.60% |
AA: 24.56% | |||||||
GG: 50.88% | |||||||
NOS3 | nitric oxyde synthse 3 | 163,729 | chr7:150991055 | rs1799983 | c.894G>T | 0.18 (T) | GT: 35.09% |
TT: 14.03% | |||||||
CC: 45.61% | |||||||
PICALM | phosphatidylinositol binding clathrin assembly protein | 603,025 | chr11:86157598 | rs3851179 | g.85868640T>C | 0.31 (T) | CT: 42.11% |
TT: 12.28% | |||||||
GG: 19.30% | |||||||
PRNP | prion protein | 176,640 | chr20:4686093 | rs1799990 | c.385A>G | 0.73 (A) | AG: 40.35% |
AA: 40.35% | |||||||
TT: 22.80% | |||||||
PSEN1 | presenilin 1 | 104,311 | chr14:73136434 | rs165932 | c.856+16G>T | 0.43 (G) | GT: 35.09% |
GG: 42.11% | |||||||
GG: 73.68% | |||||||
TNF | tumor necrosis factor | 191,160 | chr6:31575566 | rs1800629 | c.-308G>A | 0.09 (A) | GA: 22.81% |
AA: 3.51% |
Gene Symbol | Gene Name | OMIM | Location | dbSNP ID | Polymorphism | MAF | Genotype |
---|---|---|---|---|---|---|---|
CC: 18.70% | |||||||
ACE | angiotensin I converting enzyme | 106,180 | chr17:63486920 | rs4332 | c.496-66T>C | 0.47 (T) | CT: 39.81% |
TT: 41.49% | |||||||
CC: 11.46% | |||||||
AGT | Angiotensinogen | 106,150 | chr1:230710231 | rs4762 | c.620C>T | 0.10 (T) | CT: 21.96% |
TT: 66.58% | |||||||
TT: 21.97% | |||||||
AGT | Angiotensinogen | 106,150 | chr1:230710048 | rs699 | c.803T>C | 0.30 (T) | TC: 56.48% |
CC: 21.61% | |||||||
CC: 29.03% | |||||||
APOB | apolipoprotein B | 107,730 | chr2:21009323 | rs693 | c.2488C>T | 0.25 (T) | CT: 47.64% |
TT: 23.33% | |||||||
CC: 78.94% | |||||||
APOC3 | apolipoprotein C-III | 107,720 | chr11:116832924 | rs5128 | c.3175C>G | 0.23 (C) | CG: 17.60% |
GG: 3.46% | |||||||
*2*2: 0.32% | |||||||
*2*3: 7.62% | |||||||
APOE | apolipoprotein E | 107,741 | chr19:44908822 | rs7412 | c.4070C>T | 0.08 (T) | *2*4: 1.28% |
chr19:44908684 | rs429358 | c.3932T>C | 0.15 (C) | *3*3: 63.73% | |||
*3*4:23.88% | |||||||
*4*4: 3.17% | |||||||
GG: 37.39% | |||||||
CETP | cholesteryl ester transfer protein | 118,470 | chr16:56962376 | rs708272 | c.+279G>A | 0.38 (A) | GA: 49.42% |
AA: 13.19% | |||||||
GG: 96.41% | |||||||
F2 | coagulation factor II, thrombin | 176,930 | chr11:46739505 | rs1799963 | c.20210G>A | 0.01 (A) | GA: 3.47% |
AA: 0.12% | |||||||
GG: 98.02% | |||||||
F5 | coagulation factor V | 227,400 | chr1:169549811 | rs6025 | c.1691G>A | 0.01 (A) | GA: 1.61% |
AA: 0.37% | |||||||
TT: 4.59% | |||||||
IL1B | interleukin 1 beta | 147,720 | chr2:112832813 | rs1143634 | c.3954T>C | 0.13 (T) | TC: 31.39% |
CC: 64.02% | |||||||
GG: 39.95% | |||||||
IL6 | interleukin 6 | 147,620 | chr7:22727026 | rs1800795 | c.-174G>C | 0.14 (C) | GC: 43.55% |
CC: 16.50% | |||||||
GG: 81.12% | |||||||
IL6 | interleukin 6 | 147,620 | chr7:22726627 | rs1800796 | c.-573G>C | 0.31 (C) | GC: 15.90% |
CC: 2.98% | |||||||
AA: 34.41% | |||||||
IL6R | interleukin 6 receptor | 147,880 | chr1:154454494 | rs2228145 | c.1510A>C | 0.36 (C) | AC: 49.69% |
CC: 15.90% | |||||||
CC: 76.02% | |||||||
LPL | lipoprotein lipase | 609,708 | chr8:19962213 | rs328 | c.1421C>G | 0.09 (G) | CG: 20.00% |
GG: 3.98% | |||||||
CC: 38.90% | |||||||
MTHFR | methylenetetrahydrofolate reductase | 607,093 | chr1:11796321 | rs1801133 | c.665C>T | 0.25 (T) | CT: 45.84% |
TT: 15.26% | |||||||
AA: 50.36% | |||||||
MTHFR | methylenetetrahydrofolate reductase | 607,093 | chr1:11794419 | rs1801131 | c.1286A>C | 0.25 (C) | AC: 39.90% |
CC: 9.74% | |||||||
GG: 39.54% | |||||||
NOS3 | nitric oxyde synthse 3 | 163,729 | chr7:150991055 | rs1799983 | c.894G>T | 0.18 (T) | GT: 47.67% |
TT: 12.79% | |||||||
GG: 73.79% | |||||||
TNF | tumor necrosis factor | 191,160 | chr6:31575566 | rs1800629 | c.-308G>A | 0.09 (A) | GA: 22.86% |
AA: 3.35% |
Drug | Properties | Pharmacogenetics |
---|---|---|
Name:Aducanumab, BIIB-037, Aduhelm, 1384260-65-4 IUPAC Name: Immunoglobulin G1, anti-(human.beta.-amyloid) (human monoclonal biib037 heavy chain), disulfide with human monoclonal biib037.kappa.-chain, and dimer Molecular Formula: C6472H10028N1740O2014S46 Molecular Weight: 145910.3123 g/mol Category: Monoclonal antibody (mAb), anti-amyloid beta A4 protein Mechanism: Monoclonal IgG1 antibody that binds to amyloid-β, reducing amyloid plaques in the brain Effect: Anti-amyloid beta A4 protein slowing the rate of progression of Alzheimer’s disease and levels of p-tau in the cerebrospinal fluid | Pathogenic genes: APP, APOE, PSEN1, PSEN2 Mechanistic genes: Drug metabolism-related genes: -Substrate: -Inhibitor: Transporter genes: Pleiotropic genes: APOE, IL6, IL1B, TNF | |
Name: Donepezil hydrochloride, Aricept, 120011-70-3, Donepezil HCl, BNAG, E-2020, and E2020 IUPAC Name: 2-[(1-benzylpiperidin-4-yl)methyl]-5,6-dimethoxy-2,3-dihydroinden-1-one;hydrochloride Molecular Formula: C24H30ClNO3 Molecular Weight: 415.9529 g/mol Category: Cholinesterase inhibitor Mechanism: Centrally active, reversible acetylcholinesterase inhibitor; increases the acetylcholine available for synaptic transmission in the CNS Effect: Nootropic agent, cholinesterase inhibitor, and parasympathomimetic effect | Pathogenic genes: APP, APOE, CHAT Mechanistic genes: ACHE, BCHE, CHAT, CHRNA7 Drug metabolism-related genes: -Substrate: CYP2D6 (major), CYP3A4 (major), UGTs, ACHE -Inhibitor: ABCB1, ACHE, BCHE, hERG Transporter genes: ABCB1, ABCA1, ABCG2, SCN1A Pleiotropic genes: APOE, PLP, MAG, MBP, CNPase, MOG | |
Name: Galantamine hydrobromide: Galanthamine hydrobromide, 1953-04-4, Nivalin, Razadyne, UNII-MJ4PTD2VVW, and Nivaline IUPAC Name: (1S,12S,14R)-9-methoxy-4-methyl-11-oxa-4-azatetracyclo [8.6.1.0^{1,12}.0^{6,17}]heptadeca-6,8,10(17),15-tetraen-14-ol Molecular Formula: C17H22BrNO3 Molecular Weight: 368.26548 g/mol Category: Cholinesterase inhibitor Mechanism: Reversible and competitive acetylcholinesterase inhibition leading to an increased concentration of acetylcholine at cholinergic synapses; modulates nicotinic acetylcholine receptor; may increase glutamate and serotonin levels Effect: Nootropic agent, cholinesterase inhibitor, and parasympathomimetic effect | Pathogenic genes: APOE, APP Mechanistic genes: ACHE, BCHE, CHRNA4, CHRNA7, CHRNB2, SLC18A3 Drug metabolism-related genes: -Substrate: ABCB1, CYP2D6 (major), CYP3A4 (major), UGT1A1 -Inhibitor: ACHE, BCHE Transporter genes: ABCB1, SLC18A3 | |
Name: Memantine Hydrochloride, 41100-52-1, Namenda, Memantine HCL, Axura, 3,5-Dimethyl-1-adamantanamine hydrochloride, and 3,5-dimethyladamantan-1-amine hydrochloride IUPAC Name: 3,5-dimethyladamantan-1-amine;hydrochloride Molecular Formula: C12H22ClN Molecular Weight: 215.76278 g/mol Category: N-Methyl-D-Aspartate receptor antagonist Mechanism: Binds preferentially to NMDA receptor-operated cation channels; may act by blocking actions of glutamate, mediated in part by NMDA receptors Effect: Dopamine agent, antiparkinson agent, excitatory amino acid antagonist, and antidyskinetic | Pathogenic genes: APOE, MAPT, PSEN1 Mechanistic genes: CHRFAM7A, DLGAP1, FOS, GRIN2A, GRIN2B, GRIN3A, HOMER1, HTR3A Drug metabolism-related genes: -Inhibitor: CYP1A2 (weak), CYP2A6 (weak), CYP2B6 (strong), CYP2C9 (weak), CYP2C19 (weak), CYP2D6 (strong), CYP2E1 (weak), CYP3A4 (weak), NR1I2 Transporter genes: NR1I2 Pleiotropic genes: APOE, MAPT, MT-TK, PSEN1 | |
Name: Rivastigmine tartrate, 129101-54-8, SDZ-ENA 713, Rivastigmine hydrogentartrate, Rivastigmine Hydrogen Tartrate, ENA 713, and ENA-713 IUPAC Name: (2R,3R)-2,3-dihydroxybutanedioic acid;[3-[(1S)-1-(dimethylamino)ethyl]phenyl] N-ethyl-N-methylcarbamate Molecular Formula: C18H28N2O8 Molecular Weight: 400.42352 g/mol Category: Cholinesterase inhibitor Mechanism: Increases acetylcholine in CNS through reversible inhibition of its hydrolysis by acetylcholinesterase Effect: Neuroprotective agent, cholinesterase inhibitor, and cholinergic agent | Pathogenic genes: APOE, APP, CHAT Mechanistic genes: ACHE, BCHE, CHAT, CHRNA4, CHRNB2, SLC18A3 Drug metabolism-related genes: -Substrate: UGT1A9, UGT2B7 -Inhibitor: ACHE, BCHE Transporter genes: SLC18A3 Pleiotropic genes: APOE, MAPT | |
Name: Tacrine Hydrochloride, Tacrine HCl, 1684-40-8, Hydroaminacrine, tacrine.HCl, 9-AMINO-1,2,3,4-TETRAHYDROACRIDINE HYDROCHLORIDE, and Tenakrin IUPAC Name: 1,2,3,4-tetrahydroacridin-9-amine;hydrochloride Molecular Formula: C13H15ClN2 Molecular Weight: 234.7246 g/mol Category: Cholinesterase inhibitor Mechanism: Elevates acetylcholine in cerebral cortex by slowing degradation of acetylcholine Effect: Nootropic agent, cholinesterase inhibitor, and parasympathomimetic effect | Pathogenic genes: APOE Mechanistic genes: ACHE, BCHE, CHRNA4, CHRNB2 Drug metabolism-related genes: -Substrate: CYP1A2 (major), CYP2D6 (minor), CYP3A4 (major), CES1, GSTM1, GSTT1 -Inhibitor: ACHE, BCHE, CYP1A2 (weak) Transporter genes: ABCB4, SCN1A Pleiotropic genes: APOE, LEPR, MTHFR | |
| Name: (-)-Huperazine A, Huperzine A; Huperzine-A; 102518-79-6; (-)-Huperzine A; (+/−)-Huperzine A IUPAC name: (1R,9R,13E)-1-amino-13-ethylidene-11-methyl-6-azatricyclo[7.3.1.02,7]trideca-2(7),3,10-trien-5-one Molecular Formula: C15H18N2O Molecular Weight: 242.32g/mol Category: Neuroprotectanct, Cholinesterase Inhibitor Mechanism: Increases acetylcholine in the brain by inhibiting acetylcholinesterase and slowing acetylcholine hydrolysis Effect: Neuroprotective, acetylcholinesterase inhibitor, cognitive enhancer, and antiepileptic | Pathogenic genes: APP, APOE Mechanistic genes: ACHE Drug metabolism-related genes: -Substrate: ABCB1, CYP1A2, CYP3A1, CYP3A2, CYP2C11, CYP2E1, CES1, CES2 -Inhibitor: ACHE -Inducer: CYP1A2 Transporter genes: ABCB1, ABCG2 Pleiotropic genes: APOE, BDNF |
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Cacabelos, R.; Naidoo, V.; Martínez-Iglesias, O.; Corzo, L.; Cacabelos, N.; Pego, R.; Carril, J.C. Personalized Management and Treatment of Alzheimer’s Disease. Life 2022, 12, 460. https://doi.org/10.3390/life12030460
Cacabelos R, Naidoo V, Martínez-Iglesias O, Corzo L, Cacabelos N, Pego R, Carril JC. Personalized Management and Treatment of Alzheimer’s Disease. Life. 2022; 12(3):460. https://doi.org/10.3390/life12030460
Chicago/Turabian StyleCacabelos, Ramón, Vinogran Naidoo, Olaia Martínez-Iglesias, Lola Corzo, Natalia Cacabelos, Rocío Pego, and Juan C. Carril. 2022. "Personalized Management and Treatment of Alzheimer’s Disease" Life 12, no. 3: 460. https://doi.org/10.3390/life12030460