ArticleBMC genomics2023
Genome-wide association study of abnormal elevation of ALT in patients exposed to atabecestat.
Article in BMC genomics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
3 citing papers in PubMed, 1 synthesis or guideline pooled it, 5 citations in OpenAlex.
- GWAS meta-analysis of cerebrospinal fluid Alzheimer's biomarkers reveals loci regulating lipids, brain volume and autophagy.Nature communications · 2026Pooled it
- Bioactivation of the β-Amyloid Precursor Protein-Cleaving Enzyme 1 Inhibitor Atabecestat Leads to Protein Adduct Formation on Glutathione S-Transferase Pi.Chemical research in toxicology · 2025Article
- Selective HLA Class II Allele-Restricted Activation of Atabecestat Metabolite-Specific Human T-Cells.Chemical research in toxicology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAtabecestat, a potent brain penetrable BACE1 inhibitor that reduces CSF amyloid beta (Aβ), was developed as an oral treatment for Alzheimer's disease (AD). Elevated liver enzyme adverse events were reported in three studies although only one case met Hy's law criteria to predict serious hepatotoxicity.
methodWe performed a case-control genome-wide association study (GWAS) to identify genetic risk variants associated with liver enzyme elevation using 42 cases with alanine transaminase (ALT) above three times the upper limit of normal (ULN) and 141 controls below ULN. Additionally, we performed a GWAS using continuous maximal ALT/ULN (expressed as times the ULN) upon exposure to atabecestat as the outcome measure (n = 285).
resultsNo variant passed the genome-wide significance threshold (p = 5 × 10
conclusionThe suggestive GWAS signals in the case-control GWAS analysis suggest the potential role of inflammation in atabecestat-induced liver enzyme elevation.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.