ArticleLife (Basel, Switzerland)2025
Molecular Dynamics of Apolipoprotein Genotypes APOE4 and SNARE Family Proteins and Their Impact on Alzheimer's Disease.
Article in Life (Basel, Switzerland), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
1 citing paper in PubMed.
- Ontological Analysis of Brain Proteostasis Highlights the Sex-Dependent Trajectory of ApoE Isoform-Specific Regulation.bioRxiv : the preprint server for biology · 2026Article
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.
Funding
Abstract
Alzheimer's disease is a chronic neurodegenerative disorder characterized by progressive memory loss and a significant impact on quality of life. The APOE ε4 allele is a major genetic contributor to AD pathogenesis, with synaptic dysfunction being a central hallmark in its pathophysiology. While the role of APOE4 in reducing SNARE protein levels has been established, the underlying molecular mechanisms of this interaction remain obscure. Our research employs molecular dynamics simulations to analyze interactions between APOE4 and APOE3 isoforms and the synaptic proteins VAMP2, SNAP25, and SYNTAXIN1, which play crucial roles in the presynaptic membrane. Our findings reveal that APOE4 significantly destabilizes the SNARE complex, suppresses its structural dynamics, and reduces hydrogen bonding, consequently partially hindering neurotransmitter release-a very likely discovery for elucidating synaptic dysfunction in Alzheimer's disease. We identified that APOE4 exhibits a diminished affinity for the SNARE complex in comparison to APOE3. This observation suggests that APOE4 may play a role in modulating the stability of the SNARE complex, potentially impacting the progression and occurrence of Alzheimer's disease through free energy analysis. This work highlights the perturbations in synaptic function mediated by APOE4, which may offer novel insights into the molecular underpinnings of AD. By elucidating the molecular interplay between APOE4 and the SNARE complex, our study not only enhances our comprehension of AD's synaptic pathology but also paves the way for devising innovative therapeutic interventions, such as targeting the APOE4-SNARE complex interaction or to restore neurotransmitter release.
Indexed as
Identifiers
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.