Role of INPP5D, PTK2B, ZCWPW1 and TREM 2 in Predicting Risk of Progression in Cognitively Impaired Subjects to Alzheimer's Disease (P5.166)
Bibliographic record
Abstract
Objective: To examine the correlation between four risk loci and clinical progression to Alzheimer's Disease. Background: Recent genome-wide association studies have identified several new genetic risk loci for Alzheimer's Disease (AD), including INPP5D (rs35349669), PTK2B (rs28834970), ZCWPW1 (rs1476679) and TREM2 (rs75932628). Their utility in predicting outcome of patients with cognitive impairment has not been examined. We used two large Canadian cohorts to study the role of these genes in predicting the outcome of patients with cognitive impairment. Methods: In the current analysis, we compared genotype frequency in cognitively stable patients diagnosed as not cognitively impaired (NCI) or cognitively impaired no dementia (CIND) but never declined over the duration of study, to those who progressed to AD. Single nucleotide polymorphisms genotypes for INPP5D, PTK2B, ZCWPW1 and TREM 2 were obtained using TaqMan assays. Genotype frequencies were examined with chi-square tests, and odds ratios were calculated by multivariate logistic regression with age, sex, education, and APOE e4 status as covariates. Results: Within the 2 cohorts, 401 subjects who remained cognitively normal until at the end of the cohort study were used as controls, while 348 diagnosed with AD were cases. Of the 4 SNPs examined in this study, only PTK2B was significant (p=0.042). When we compared the genotypic frequencies between subjects with CIND who remained stable vs. those who progressed to AD (n=134), the significance is even stronger (p<0.001), with an O.R. of 1.75 (95[percnt] C.I 1.13-2.71), which remains constant after adjustment with age, sex, and APOE e4 carrier status. Conclusions: We found that only the PTK2B risk allele was significantly associated with progression from cognitive impairment, which is independent from the effect of age and APOE genotype. These findings contribute to our understanding of the pathogenesis of AD, which may help develop potential novel biomarkers and therapeutic targets.
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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 | 0.001 |
| 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) | 0.001 | 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".