Associations between 5‐lipoxygenase activating protein (FLAP) genetic variation rs9551963 and Alzheimer’s disease phenotypes
Bibliographic record
Abstract
Abstract Background Leukotrienes are inflammatory mediators, synthesized by 5‐lipoxygenase and its activating protein (FLAP), and their activity may play a role in Alzheimer’s disease (AD). In AD mouse models, inhibition of FLAP improved memory and reduced amyloid (Aβ) deposition. Single nucleotide polymorphisms (SNPs) of ALOX5AP, which encodes FLAP, have been implicated in ischemic stroke in humans. However, there is limited research on the relationship between ALOX5AP and AD. This longitudinal study investigated associations between the ALOX5AP SNP rs9551963 A/C and various AD phenotypes. Method Participants from the Alzheimer’s Disease Neuroimaging Initiative (phases GO, 2, and 3) diagnosed with AD, mild cognitive impairment (MCI), or clinically normal cognition (CN) were categorized as minor allele carriers (AC, CC) or non‐carriers (AA) of rs9551963. Mini Mental State Exam (MMSE) and Rey Auditory Verbal Learning Test (RAVLT) % forgetting were selected to assess cognition. Cerebrospinal fluid biomarkers and MRI brain volumetric data were also considered. Interactions between rs9551963 genotype and time (baseline, month 24, and month 48) were measured in mixed models. All models controlled for age, sex, and APOE e4 status; education and baseline intracranial volume were additional controls in cognitive and volumetric analyses respectively. Result Minor allele carriers in the AD‐MCI Aβ‐positive group had worse decline on the MMSE (F1,297 = 5.33, p = 0.022, n = 521), and smaller volumes of whole brain (F1,146 = 7.13, p = 0.008, n = 408) and hippocampus (F1,132 = 6.38, p = 0.013, n = 377) over time that were not seen in other subgroups. In the AD subgroup, Aβ‐positive carriers had greater increases in RAVLT % forgetting scores (F1,135.5 = 6.19, p = 0.014, n = 158) and greater whole brain volume loss (F1,27.6 = 5.67, p = 0.024, n = 132), over time. These associations were not seen in Aβ‐negative participants. Conclusion Minor allele carriers of the ALOX5AP SNP rs9551963 who were Aβ‐positive showed greater loss of cognitive status and memory, and more hippocampal and whole brain atrophy, over time. These findings suggest a possible effect of leukotriene synthesis in the progression of AD.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 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) | 0.006 | 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".