Polymorphisms at the Paraoxonase 1 L55M and Q192R Loci Affect the Pathophysiology of Alzheimer’s Disease: Emphasis on the Cholinergic System and Beta-Amyloid Levels
Bibliographic record
Abstract
BACKGROUND: Paraoxonase 1 (PON1) functions to protect the cholinergic system against nerve gases and the organophosphate family of pesticides. Recent studies have shown that polymorphisms at the PON1 L55M and Q192R loci might affect individual susceptibility to experience-derived and environmental events such as the exposure to inhibitors of cholinesterase (ChEIs). OBJECTIVE: ChEI therapy being the treatment of choice for mild-to-moderate Alzheimer's disease (AD) patients, we determined whether genetic variations in the PON1 loci are associated with AD risk and whether they affect brain choline acetyltransferase (CHAT) activity, nicotinic receptor density, and beta-amyloid (Abeta) levels in different regions of AD and age-matched control subjects. METHODS: This pilot genetic study used a small cohort of brains from autopsy-confirmed AD patients and age-matched controls from the Douglas Hospital Brain Bank, Quebec, Canada. RESULTS: The frequency of the M55M genotype at the PON1 L55M locus was found to be significantly increased in AD patients relative to age-matched controls (p < 0.05). Significant associations were observed between the PON1 L55M and Q192R polymorphisms and frontal cortex Abeta levels as well as CHAT activity and nicotinic receptor density in the temporal cortex. CONCLUSIONS: Our results suggest a prominent role for PON1 in the pathophysiology of common AD with a marked impact on the cholinergic system and Abeta levels in the brain.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| 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) | 0.003 | 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".