Mass spectrometry imaging of gangliosides in Alzheimer's Disease
Bibliographic record
Abstract
Lipid dysregulation is a core component of neurodegeneration in Alzheimer's Disease (AD). Gangliosides are members of the glycosphingolipid family enriched in the central nervous system. The healthy brain maintains a homeostatic balance of gangliosides. GM1, the most abundant ganglioside in the adult brain, is enriched within neuronal membrane rafts and exerts neuroprotective effects. In contrast, accumulation of GM2 and GM3, degradative by-products of GM1, can directly cause neurodegeneration, suggesting that ganglioside dysregulation is a key contributor in AD pathology. Our current gap in knowledge is whether ganglioside dysregulation is worsened by, or contributes, to beta-amyloid (Aβ) accumulation in the brain. Thus, anatomical-specific distributions of gangliosides were investigated in the amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mouse model of AD that develops age-dependent Aβ plaques. Hypothesis: Aβ accumulation leads to increased levels of simple gangliosides GM2 and GM3 contributing to neurodegeneration in the AD brain. Methods: Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) was performed on brains of wildtype and transgenic mice aged 4, 8, 12, and 18 months to quantify ganglioside distribution across anatomical regions. Results: Our data demonstrate an age-dependent increase in simple gangliosides that are exacerbated in the Tg mice. Aged Tg mice showed higher levels of simple gangliosides as compared to Wt in the cortex and hippocampus, brain regions of initial amyloid deposition. Significance: This work identifies a potential interplay between Aβ and simple gangliosides in driving neurodegeneration, highlighting a rationale for evaluating glycosphingolipid modifying approaches in AD treatment.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".