P1‐160: Cerebral glucose metabolism in a 5XFAD butyrylcholinesterase‐knockout mouse model of Alzheimer's disease
Bibliographic record
Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder that causes dementia. Characteristic hallmarks of AD include the deposition of pathological β-amyloid plaques (Aβ) and neurofibrillary tangles (NFT) in the brain. The AD brain also exhibits cholinergic dysfunction; loss of cholinergic neurons contributes to the cognitive and behavioural symptoms of AD. Furthermore, cholinesterases such as butyrylcholinesterase (BuChE) associate with Aβ and NFT pathology. Recent work in our lab involving a novel BuChE knock-out mouse model of AD (5XFAD/BuChE-KO) has revealed that the absence of BuChE expression leads to diminished fibrillar forms of Aβ pathology in the brain. However, the exact role of BuChE on brain function in AD has not been determined. To further elucidate the effects of BuChE on metabolic regulation (thus brain function) in AD, we assessed cerebral glucose metabolism in this 5XFAD/BuChE-KO model using FDG-PET. Male 5XFAD/BuChE-KO mice (n=5) and age-matched BuChE-KO wild type controls (n=2) at 5 months underwent PET scanning 30 min after FDG administration and subsequently imaged using CT and MRI. Whole brain ROIs were generated from co-registered PET/CT/MRI data. FDG standardized uptake values (SUVs) were then compared between 5XFAD/BuChE-KO and BuChE-KO groups. At 5 months, significant Aβ deposition was present in the 5XFAD/BuChE-KO mouse brain. 5XFAD/BuChE-KO animals demonstrated a 23% decrease in whole brain SUVs compared to BuChE-KO controls (p=0.037). This significant decrease had not been observed in our previous investigations of cerebral metabolism in a BuChE expressing 5XFAD model (vs. control counterparts) at 5 months. We have previously observed variation in cerebral glucose metabolism with Aβ pathology in 5XFAD mice. Our current investigations suggest that BuChE may also be a modulator of cerebral glucose metabolism in AD, whereby the presence/absence of BuChE could significantly impact not only pathology but also brain function over the course of AD. Comparison of these 5XFAD/BuChE-KO brain metabolism results with those in BuChE expressing 5XFAD counterparts is currently underway. Furthermore, regional assessment of brain metabolism and corroborating neuropathology in these animals may further implicate BuChE in the progression of AD and may highlight the potential role of targeted BuChE imaging approaches for AD diagnostics.
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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) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".