Figure 1.
Updated AT(N) Classification According to NIA-AA (2024)
| Category | Symbol | Biomarker Type | Example Markers | Detection Method |
|---|---|---|---|---|
| A | A+/A– | β-amyloid | ↓ Aβ42 (CSF), ↓ Aβ42/Aβ40 (plasma), Positive amyloid PET | CSF (ELISA, mass spectrometry), Plasma (Simoa), PET |
| T | T+/T– | Phosphorylated tau | ↑ p-tau181, ↑ p-tau217 (CSF, plasma), Positive tau PET | CSF, Plasma (Simoa), PET (e.g., flortaucipir) |
| N | N+/N– | Neurodegeneration | ↑ t-tau (CSF), ↑ NfL, ↑ GFAP (plasma), brain atrophy on MRI, ↓ FDG-PET | CSF, Plasma, MRI, FDG-PET |
| (G) | G+/G– | Gliosis / Neuroinflammation | ↑ GFAP, ↑ YKL-40, ↑ TREM2 | CSF, Plasma (Simoa, ELISA) |
Comparison of Anti-Aß Antibody Trials: Efficacy, Safety, and Clinical Significance Sources: [24,29, 32, 35–37, 53]
| Study (Year) | Antibody | Number of Patients | Mean Effect (vs Placebo) | p-value | 95% Cl | ARIA-E/ARIA-H (%) | Effect (%) | Duration (months) | Clinical Significance |
|---|---|---|---|---|---|---|---|---|---|
| EMERGE (2022) | Aducanumab (high dose) | 1638 | –0,39 | 0,012 | –0,69 to –0,09 | – | 22% (slowing) | 18 | Yes (moderate slowing) |
| ENGAGE (2022) | Aducanumab (high dose) | 1647 | 0,03 | 0,833 | –0,26 to +0,33 | – | –2% (no effect) | 18 | No significant effect |
| Clarity AD (2022) | Lecanemab | 1795 | –0,45 | <0,001 | –0,67 to –0,23 | 12,6/– | ~27% (slowing) | 18 | Yes (moderate slowing) |
| TRAILBLAZ-ER-ALZ2 (2023) | Donanemab | 1736 | 3,25 (¡ADRS) | <0,001 | 1,88 to 4,62 | 24,0/31,4 | 35% (slowing) | 18 | Yes (substantial slowing) |
| GRADUATE 1 (2023) | Gantenerumab | 985 | –0,31 | 0,1 | –0,66 to 0,05 | 24,9/– | ~8% (not significant) | 27 | No significant effect |
| GRADUATE II (2023) | Gantenerumab | 980 | –0,19 | 0,3 | –0,55 to 0,17 | 24,9/– | ~6% (not significant) | 27 | No significant effect |
| EXPEDITION 1/2 (2014) | Solanezumab | 2052 | –0,8 (ADAS-cog) | 0,24 | –2,1 to 0,5 | 0,9/4,9 | ~O% (no effect) | 18 | No clinical effect |
| EXPEDITION 3 (2018) | Solanezumab | 2129 | –0,8 (ADAS-cog 14) | 0,1 | –1,73 to 0,14 | ~0,1/– | ~11% (no effect) | 19 | No clinical effect |
| DIAN-TU-001 (2024) | Gantenerumab/Solanezumab | 142 | – (b¡omarker-only study) | – | – | – | – | 48 | No clinical effect |
Comparison of Sensitivity and Specificity of Selected Biomarkers in the Diagnosis of Alzheimer’s Disease
| Biomarker | Sample Type / Method | Sensitivity (%) | Specificity (%) | Notes |
|---|---|---|---|---|
| Aβ42 / Aβ42:Aβ40 | CSF | 85–95 | 80–90 | Decreased Aβ42 correlates with β-amyloid deposition |
| Aβ42:Aβ40 | Blood (plasma) | 80–88 | 70–85 | Strong correlation with amyloid PET; easily accessible, but not standardized |
| p-tau181 | CSF | 85–90 | 85–90 | Correlates with tau pathology and clinical progression |
| p-tau217 | Blood (plasma) | 89–94 | 90–96 | Highest specificity for differentiating AD from other dementias |
| NfL | Blood (plasma)/CSF | 75–85 | 60–70 | Nonspecific – elevated in many neurodegenerative diseases |
| GFAP | Blood (plasma) | 80–85 | 75–85 | Correlates with astroglial activation and amyloid pathology |
| Amyloid PET | Imaging | 90–95 | 85–95 | High accuracy; expensive and limited availability |
| Tau PET | Imaging | 85–90 | 85–90 | Accurate for assessing spread of tau pathology; limited availability |