P1‐150: Aerobic Glycolysis in the Frontal Cortex Correlates With Memory Performance in Wild‐Type Mice But Not the APP/PS1 Mouse Model of Cerebral Amyloidosis
Bibliographic record
Abstract
Approximately 10 percent of glucose in the brain is exclusively metabolized by glycolysis to generate lactate, even when oxygen is not rate limiting. This form of metabolism is known as aerobic glycolysis. Lactate, the end product of aerobic glycolysis, plays a key role in long-term memory, yet the role of this metabolite in the cognitive decline associated with Alzheimer's disease (AD) remains poorly understood. Here we examined the relationship between cerebral lactate levels and memory performance over a 12 month period in an APP/PS1 mouse model of AD which progressively accumulates amyloid-β (Aβ). In vivo H-magnetic resonance spectroscopy (H-MRS) was used to measure cerebral lactate levels while microdialysis was used to measure lactate levels in the interstitial fluid of the hippocampus. Immunoblot analysis was performed to measure protein expression of lactate-producing, -consuming, or -transporting enzymes in the frontal cortex. Immunofluorescence staining of brain sections was used to examine the spatial expression of aerobic glycolysis enzymes. Memory was assessed using the Morris Water Maze. In vivo H-MRS analysis revealed an age-dependent decline in lactate levels within the frontal cortex of control mice whereas lactate levels remained unaltered in APP/PS1 mice from 3 to 12 months of age. Microdialysis of hippocampal interstitial fluid revealed elevated lactate levels in aged APP/PS1 mice relative to wildtype mice. We also observed that increased expression of lactate producing enzymes in the frontal cortex correlated with better memory performance, whereas expression of LDHB, a lactate consuming enzyme, correlated with poorer memory. Interestingly, in APP/PS1 mice the opposite effect was detected where increased expression of lactate producing enzymes correlated with poorer memory performance. In addition, immunofluorescent staining of brain sections revealed expression of the aerobic glycolysis enzymes PDK1 and LDHA primarily in neurons in control mice, as well as in astrocytes surrounding amyloid plaques in APP/PS1 mice. These observations collectively indicate that production of lactate through aerobic glycolysis is beneficial for memory function in healthy mice but declines naturally with age. In contrast, elevated lactate levels in APP/PS1 mice indicate perturbed lactate processing; a factor that may contribute to AD pathogenesis.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".