ArticleNature communications2024
Altered expression of Presenilin2 impacts endolysosomal homeostasis and synapse function in Alzheimer's disease-relevant brain circuits.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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
13 citing papers in PubMed.
- Synaptic Proteostasis in Health and Disease.Journal of neurochemistry · 2026Review
- HSPA8 orchestrates SNARE complex assembly to drive extracellular vesicle-mediated spread of p-tau217 in Alzheimer's disease.Translational neurodegeneration · 2026Article
- Entorhinal Astrocyte Transplants Restore Spatial Exploration and Alleviate Amyloid-Beta Pathology in Alzheimer's Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Phycocyanobilin Attenuates Oligomerized Amyloid β-Induced Neuronal Senescence Through SIRT1-Associated Mechanisms.Nutrients · 2026Article
- Synaptojanin-2-binding protein ameliorates oxidative stress, neuroinflammation and depression-like behaviors via SYNJ2/PIPRedox biology · 2026Article
- Brain-targeted delivery of siRNA via non-viral delivery systems, the therapeutic strategy for Alzheimer's disease-Unveiling challenges and prospects.International journal of pharmaceutics: X · 2026Review
- Dysregulated mRNA Translation in Alzheimer's Disease: Mechanisms, Therapeutic Opportunities, and Challenges for Clinical Translation.Clinical interventions in aging · 2026Review
- Article
- Circadian rhythms of neuronal and astrocytic glutamate transporters in the suprachiasmatic nucleus of mice.Frontiers in cellular neuroscience · 2026Article
- Spectrum of γ-Secretase dysfunction as a unifying predictor of ADAD age at onset across PSEN1, PSEN2 and APP causal genes.Molecular neurodegeneration · 2025Article
- Lysosome repair fails in ageing and Alzheimer's disease.Nature cell biology · 2025Article
- The curious case of a heterozygous loss-of-functionMolecular neurodegeneration advances · 2025Article
- γ-secretase targeting in Alzheimer's disease.Journal of Alzheimer's disease reportsReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
Abstract
Rare mutations in the gene encoding presenilin2 (PSEN2) are known to cause familial Alzheimer's disease (FAD). Here, we explored how altered PSEN2 expression impacts on the amyloidosis, endolysosomal abnormalities, and synaptic dysfunction observed in female APP knock-in mice. We demonstrate that PSEN2 knockout (KO) as well as the FAD-associated N141IKI mutant accelerate AD-related pathologies in female mice. Both models showed significant deficits in working memory that linked to elevated PSEN2 expression in the hippocampal CA3 region. The mossy fiber circuit of APPxPSEN2KO and APPxFADPSEN2 mice had smaller pre-synaptic compartments, distinct changes in synaptic vesicle populations and significantly impaired long term potentiation compared to APPKI mice. At the cellular level, altered PSEN2 expression resulted in endolysosomal defects and lowered surface expression of synaptic proteins. As PSEN2/γ-secretase is restricted to late endosomes/lysosomes, we propose PSEN2 impacts endolysosomal homeostasis, affecting synaptic signaling in AD-relevant vulnerable brain circuits; which could explain how mutant PSEN2 accelerates AD pathogenesis.
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.