Assessing Reactive Astrogliosis with <sup>18</sup>F-SMBT-1 Across the Alzheimer Disease Spectrum
Bibliographic record
Abstract
Background: Neuroinflammatory reaction in Alzheimer’s disease (AD) brains involves reactive astrocytes which overexpress monoamine oxidase-B (MAO-B). 18F-SMBT-1 is a novel F-18 PET tracer highly selective for MAO-B. We characterized the clinical performance of 18F-SMBT-1 PET across the Alzheimer’s disease (AD) continuum as a potential surrogate marker of reactive astrogliosis Methods: We assessed 18F-SMBT-1 PET regional binding in 77 volunteers (76±5.5 y.o.; 41F/36M) across the AD continuum: 57 cognitively unimpaired controls (CN, 44 Aβ- & 13 Aβ+), 12 mild cognitively impaired (MCI, 9 Aβ- & 3 Aβ+), and 8 AD dementia patients (6 Aβ+ and 2 Aβ-). All participants also underwent Aβ and tau PET imaging, 3T MRI and neuropsychological evaluation. Tau imaging results were expressed in standard uptake value ratios (SUVR) using the cerebellar cortex as reference region, while Aβ burden was expressed in Centiloids. 18F-SMBT-1 outcomes were expressed as SUVR using the subcortical white matter as reference region. Results:18F-SMBT-1 yielded high contrast images at steady state (60-80 min after injection). When compared to Aβ-CN, there were no significant differences in 18F-SMBT-1 binding in the Aβ-MCI group. Conversely, 18F-SMBT-1 binding was significantly higher in several cortical regions in the Aβ+AD group, but also was significantly lower in mesial temporal and basal ganglia. Most importantly, 18F-SMBT-1 binding was significantly higher in the same regions in Aβ+CN when compared to Aβ-CN. When all clinical groups were considered together, 18F-SMBT-1 was highly correlated with Aβ burden, and much less with tau burden. While in most cortical regions 18F-SMBT-1 was not correlated with brain volumetrics, regions known for high MAO-B concentrations presented a direct association with hippocampal and grey matter volumes, while the occipital lobe was directly associated with white matter hyperintensities. 18F-SMBT-1 binding was inversely correlated with MMSE and AIBL PACC in some neocortical regions such as the frontal cortex, lateral temporal and supramarginal gyrus. Conclusion: Cross-sectional human PET studies with 18F-SMBT-1, showed that Aβ+AD, but most importantly, Aβ+CN have significantly higher regional 18F-SMBT-1 binding than Aβ- CN. Moreover, in several regions in the brain, 18F-SMBT-1 retention was highly associated with Aβ load. These findings suggest that increased 18F-SMBT-1 binding is detectable at the preclinical stages of Aβ accumulation, providing strong support for its use as surrogate marker of astrogliosis in the AD continuum.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".