Impact of beta‐amyloid oligomers on in vivo brain glucose metabolism
Bibliographic record
Abstract
Abstract Background The deposition of β‐amyloid (Aβ) plaques is a classical neuropathological feature of Alzheimer’s disease (AD). Currently, it is believed that intermediate products of the Aβ fibrillogenesis process, like the β‐amyloid oligomers (AβOs), are the most toxic forms, and are involved in neurodegenerative processes in AD. The evaluation of cerebral glucose metabolism in patients with β‐amyloid plaque deposition using [18F]FDG‐PET has been used as a marker of neurodegeneration in AD. However, little is understood about AβOs' impact on glucose metabolism prior to Aβ plaques formation. The aim of this study was to evaluate the impact of the intracerebroventricular infusion of AβOs on in vivo glucose metabolism via [18F]FDG‐PET. Method Male Swiss mice (3‐month‐old, n = 20 per group) were divided into three groups: Vehicle, AβOs 10pmol, and AβOs 100pmol. Vehicle/AβOs were infused into mice’ right ventricle using the freehand technique after brief isoflurane anesthesia. [18F]FDG‐PET scans were performed 24h after AβOs infusion. The same animals underwent the Novel Object Recognition (NOR) task 24h after scanning. The images were processed and analyzed using MINC tools. Metabolic networks were built by computing Pearson correlation coefficients based on 2,000 bootstrap samples and FDR corrected (P<0.05). See Fig. 1a, for a experimental design illustration. Results AβOs induced dose‐dependent brain glucose hypometabolism (Fig. 1b) and metabolic network disturbances. Voxel‐wise percentage change analysis revealed moderate reductions in glucose brain metabolism (5% to 15%) following infusion of 10pmol AβOs, whereas 100 pmol AβOs led to widespread and substantial reductions of up to 25% (Fig. 1c). T‐statistical voxel‐wise analysis indicated statistically significant brain glucose hypometabolism only in the 100pmol group (Fig. 1d). The low‐dose AβOs (10pmol) induced brain inter‐region metabolic hyperconnectivity, while the 100 pmol dose caused hypoconnectivity (Fig. 1e). Furthermore, both AβOs infusion groups exhibited impaired recognition memory in the NOR task (Fig. 1f). Conclusion Our results are the first demonstration of AβOs causing in vivo glucose hypometabolism and metabolic network disturbances in the absence of plaques. These findings point to an early impact of AβOs on glucose metabolism, independent of β‐amyloid plaque formation. While the molecular pathways underlying this effect require further investigation, they may represent important AD pathophysiological mechanisms and potential targets for therapeutic intervention.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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".