IC‐P‐070: Evaluation of a radiolabelled butyrylcholinesterase ligand, N‐methyl‐4‐piperdinyl‐4‐[18F]‐fluorobenzoate, in human brain tissues
Bibliographic record
Abstract
Alzheimer's disease (AD) is a chronic, progressive neurodegenerative disorder of the brain. This disease has characteristic brain hallmarks such as β-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs). Currently, AD pathology is only discernible by post-mortem examination in order to provide definitive disease diagnosis. AD is also characterized by cholinergic dysfunction due to a decrease in the brain levels of the neurotransmitter acetylcholine. The cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), regulate levels of this neurotransmitter and in AD these enzymes, especially BuChE, have been found to be associated with Aβ plaques and NFTs. In addition, cholinesterase activity may distinguish Aβ plaques found in AD brain from those present in some cognitively normal individuals. The co-localization of cholinesterase activity with AD pathology may represent a suitable target for diagnosis and treatment monitoring of the disease during life. Currently, positron emission tomography (PET) imaging of Aβ deposits is under consideration for use in AD imaging. However, since Aβ plaques can be observed in some cognitively normal individuals, such imaging appears to be of limited specificity for AD. Co-localization of BuChE with Aβ plaques may be indicative of AD neuropathology thus, fluorine labelled PET imaging agents targeting BuChE could provide a means for non-invasive AD diagnosis during life. N -Methyl-4-piperidinyl-4-fluorobenzoate has been identified, through enzyme kinetics as being specific for BuChE over AChE. Fluorination of a precursor, N-methyl-4-piperdinyl-4-nitrobenzoate, was achieved through nucleophilic aromatic substitution using literature methodology. As such, efforts are underway to further develop 18 F-labelled N -methyl-4-piperdinyl-4-fluorobenzoate to generate in vitro autoradiographs of BuChE in human brain tissues. Comparisons will be made between AD brains and cognitively normal controls displaying Aβ pathology. It is anticipated that the BuChE-specific radioligand will differentiate between AD and non-AD brain tissues. BuChE-specific 18 F imaging agents may differentiate between Aβ plaques in AD and cognitively normal brain tissues. As such, development of cholinesterase-specific 18 F imaging agents should facilitate definitive diagnosis of AD during life.
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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) | 0.001 | 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 | 0.001 | 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".