P1‐053: Associations between TLR4 Asp299Gly variant and Alzheimer's‐related pathological biomarkers
Bibliographic record
Abstract
TLR4 is a member of the Toll-like receptor family which plays a role in pathogen recognition and activation of innate immunity. A common missense mutation (Asp299Gly) in the extracellular domain of the receptor was found in association with a blunted inflammatory response to inhaled toxins in humans. Carriage of the minor 299Gly allele seems to exert a protective effect as it was overrepresented in a Sicilian cohort of centenarians (14.6%). Conversely, the frequency of the 299Gly allele was significantly lower in LOAD cases (3.1%) compared to controls (7.2%) in an Italian population sample. The objectives of the present study are to determine the frequency of the 299Gly allele in three independent cohorts and to correlate these findings with available Alzheimer-related pathological biomarkers. Genotyping was performed with Illumina BeadChips for DNA samples from the Quebec Founder Population (QFP, n=629) and Alzheimer's Disease Neuroimaging Initiative (ADNI, n=757). For the PREVENT-AD cohort (n=152), genotyping was performed using pyrosequencing. Classic AD biomarkers were measured by ELISA using CSF samples from the PREVENT-AD and ADNI cohorts. Structural and functional magnetic resonance imaging (MRI) was undertaken for a subgroup of participants. Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was also evaluated for the PREVENT-AD cohort. In the QFP, the 299Gly allele was present in 6.3% of LOAD cases and 10.7% of aged-matched control subjects (p≤0.005). Healthy subjects enrolled in the PREVENT-AD study (with a first-degree family history of AD) were positive for the 299Gly allele in a proportion of 12.5%. In ADNI, the 299Gly allele was detected in 9.5% of AD cases, 9.9% of MCI patients and 11.2% of control subjects (baseline diagnostic, p≥0.05). Although not associated with the disease in the latter population, the 299Gly allele significantly correlated with higher CSF APOE levels measured in MCI patients. In unaffected subjects from the PREVENT-AD cohort, the 299Gly allele was significantly associated with enhanced cortical thickness and a higher RBANS visuospatial score. The presence of the 299Gly allele is clearly associated with neuroprotection. Targeting TLR4 signaling pathway could be considered for pharmacological intervention to prevent Alzheimer's disease.
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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 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".