ArticleMolecular neurodegeneration2016
Redundant Gs-coupled serotonin receptors regulate amyloid-β metabolism in vivo.
Article in Molecular neurodegeneration, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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
37 citing papers in PubMed, 79 citations in OpenAlex.
- Effect of escitalopram dose and treatment duration on CSF Aβ levels in healthy older adults: A controlled clinical trial.Neurology · 2020Trial
- Systems biology of Alzheimer's Disease: a scoping review of key pathways and mechanisms.Molecular neurodegeneration · 2026Article
- Targeting the serotonergic system in the treatment of neurodegenerative diseases-emerging therapies and unmet challenges.Pharmacological reviews · 2025Review
- The interaction between neurotransmitter receptor activity and amyloid-β pathology in Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2025Review
- Gnb5 is a negative regulator of the BACE1-mediated Aβ generation and ameliorates cognitive deficits in a mouse model of Alzheimer's disease.PLoS biology · 2025Article
- A bibliometric analysis of research on dementia comorbid with depression from 2005 to 2024.Frontiers in neuroscience · 2025Article
- High-Salt Diet Accelerates Neuron Loss and Anxiety inInternational journal of molecular sciences · 2024Article
- Systemic Modulators: Potential Mechanism for the 5-HT System to Mediate Exercise Amelioration in Alzheimer's Disease.Aging and disease · 2024Review
- Dorsal raphe nucleus-hippocampus serotonergic circuit underlies the depressive and cognitive impairments in 5×FAD male mice.Translational neurodegeneration · 2024Article
- 5-HT4 receptor agonists treatment reduces tau pathology and behavioral deficit in the PS19 mouse model of tauopathy.Frontiers in cellular neuroscience · 2024Article
- Targeted metabolomic analysis in Parkinson's disease brain frontal cortex and putamen with relation to cognitive impairment.NPJ Parkinson's disease · 2023Article
- Anxiety and Alzheimer's disease pathogenesis: focus on 5-HT and CRF systems in 3xTg-AD and TgF344-AD animal models.Frontiers in aging neuroscience · 2023Review
- Article
- Serotonin Receptor Gene Polymorphisms Are Associated with Cerebrospinal Fluid, Genetic, and Neuropsychological Biomarkers of Alzheimer's Disease.Biomedicines · 2022Article
- The effect of citalopram treatment on amyloid-β precursor protein processing and oxidative stress in human hNSC-derived neurons.Translational psychiatry · 2022Article
- Extraversion Is Associated With Lower Brain Beta-Amyloid Deposition in Cognitively Normal Older Adults.Frontiers in aging neuroscience · 2022Article
- Review of Advanced Drug Trials Focusing on the Reduction of Brain Beta-Amyloid to Prevent and Treat Dementia.Journal of experimental pharmacology · 2022Review
- Understanding How Physical Exercise Improves Alzheimer's Disease: Cholinergic and Monoaminergic Systems.Frontiers in aging neuroscience · 2022Review
- Astrocytes in depression and Alzheimer's disease.Frontiers of medicine · 2021Review
- Pimavanserin, a 5HTJournal of neurochemistry · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe aggregation of amyloid-β (Aβ) into insoluble plaques is a hallmark pathology of Alzheimer's disease (AD). Previous work has shown increasing serotonin levels with selective serotonin re-uptake inhibitor (SSRI) compounds reduces Aβ in the brain interstitial fluid (ISF) in a mouse model of AD and in the cerebrospinal fluid of humans. We investigated which serotonin receptor (5-HTR) subtypes and downstream effectors were responsible for this reduction.
resultsAgonists of 5-HT4R, 5-HT6R, and 5-HT7R significantly reduced ISF Aβ, but agonists of other receptor subtypes did not. Additionally, inhibition of Protein Kinase A (PKA) blocked the effects of citalopram, an SSRI, on ISF Aβ levels. Serotonin signaling does not appear to change gene expression to reduce Aβ levels in acute timeframes, but likely acts within the cytoplasm to increase α-secretase enzymatic activity. Broad pharmacological inhibition of putative α-secretases increased ISF Aβ and blocked the effects of citalopram.
conclusionsIn total, these studies map the major signaling components linking serotonin receptors to suppression of brain ISF Aβ. These results suggest the reduction in ISF Aβ is mediated by a select group of 5-HTRs and open future avenues for targeted therapy of AD.
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.