<i>In vivo</i> assessment of astrocyte reactivity in patients with progressive supranuclear palsy
Bibliographic record
Abstract
Abstract Emerging evidence highlights the association of reactive astrocytes with neurodegenerative diseases. Although astrocytic pathology is a pathological hallmark of progressive supranuclear palsy (PSP), its role in the pathophysiology of the disease is not fully understood. In this study, we aimed to assess astrocyte reactivity in vivo in patients with PSP using magnetic resonance spectroscopy and plasma biomarkers. Furthermore, given the central role of astrocytes in brain energy metabolism and their glycolytic profile, which implies a preference for lactate production, we investigated alterations in brain energy metabolism by measuring brain lactate levels and examined their relationship with astrocyte reactivity. We included 30 patients with PSP-Richardson’s syndrome and 30 healthy controls; in patients, tau deposition was confirmed via 18 F-florzolotau-PET. Myo-inositol, an astroglial marker, and lactate were quantified in the anterior cingulate cortex (ACC) via magnetic resonance spectroscopy. The ACC was studied because previous functional imaging studies revealed its involvement as a distinctive feature of PSP. It involves in cognitive processes, such as executive function, which often exhibit deficits in patients with PSP. We measured plasma concentrations of glial fibrillary acidic protein (GFAP) as another astrocytic marker, neurofilament light chain (NfL), and tau phosphorylated at threonine 181. Reactive astrocytes, tau deposition, and synaptic loss in the ACC were assessed in post-mortem brain samples from another three patients with PSP with comparable disease durations to those of participants. The level of myo-inositol in the ACC and the plasma GFAP were significantly higher in patients than in healthy controls; these increases were significantly associated with Frontal Assessment Battery and Mini-Mental State Examination scores, respectively. The lactate level in the ACC was high in patients and correlated significantly with high myo-inositol levels. The plasma NfL outperformed other biomarkers in discriminating patients from controls (area under the curve [AUC] = 0.95), followed by lactate and myo-inositol (AUC = 0.88 and 0.78, respectively). Histological analysis of the ACC in patients revealed evident reactive astrocytes despite mild tau deposition and no marked synaptic loss. We found high levels of astrocyte biomarkers (myo-inositol in the ACC and plasma GFAP) in patients with PSP, suggesting astrocyte reactivity, and these biomarkers correlated with cognitive decline. Elevated myo-inositol levels were associated with high lactate levels, suggesting a link between reactive astrocytes and brain energy metabolism changes. Our results indicate that astrocyte reactivity in the ACC precedes pronounced tau pathology and neurodegenerative processes in the region and affects brain function in PSP.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 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".