ArticleProceedings of the National Academy of Sciences of the United States of America2011
Serotonin signaling is associated with lower amyloid-β levels and plaques in transgenic mice and humans.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 183 papers, 3 of them syntheses 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
183 citing papers in PubMed, 3 syntheses or guidelines pooled it, 354 citations in OpenAlex.
- Efficacy of selective serotonin reuptake inhibitors-related antidepressants in Alzheimer's disease: a meta-analysis.European journal of medical research · 2024Pooled it
- Β-Amyloid Burden is Not Associated with Cognitive Impairment in Schizophrenia: A Systematic Review.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2016Pooled it
- Amyloid deposition in Parkinson's disease and cognitive impairment: a systematic review.Movement disorders : official journal of the Movement Disorder Society · 2015Pooled it
- Lower regional gray matter volume in the absence of higher cortical amyloid burden in late-life depression.Scientific reports · 2021Trial
- Effect of escitalopram dose and treatment duration on CSF Aβ levels in healthy older adults: A controlled clinical trial.Neurology · 2020Trial
- An antidepressant decreases CSF Aβ production in healthy individuals and in transgenic AD mice.Science translational medicine · 2014Trial
- Exercise and fluoxetine in Alzheimer's disease: Molecular mechanisms of synergistic and antagonistic effects (Review).International journal of molecular medicine · 2026Review
- Exploring the lung-brain axis in perioperative neurocognitive disorders: a potential therapeutic target.Molecular psychiatry · 2026Article
- Serotonergic System Dysregulation in Alzheimer's Disease.ACS chemical neuroscience · 2026Review
- Synthesis of 4-Hydroxyacetophenone-Derived Bis-Schiff Bases as Potent Cholinesterase Inhibitors: In Vitro Evaluation, Molecular Docking, DFT, and ADMET Analysis.Chemistry & biodiversity · 2026Article
- Trajectories of late-life depression: insights from molecular imaging.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Lower Plasma Serotonin is Associated with Higher Amyloid Burden, Hippocampal Atrophy, and Cognitive decline in Alzheimer's Disease: A 24-Month Longitudinal Study.Journal of molecular neuroscience : MN · 2026Article
- Sex differences in neuromodulatory subcortical systems and their implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- The Crossroads of Neurodegeneration: Exploring the Overlap Between Alzheimer's Disease and Depression.Cureus · 2026Review
- Systems biology of Alzheimer's Disease: a scoping review of key pathways and mechanisms.Molecular neurodegeneration · 2026Article
- Pharmacotherapy of major depressive disorder in older adults: from an evidence-informed stepwise algorithm to precision medicine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Relationship Between SSRI Exposure During Later Life and Clinical and Neuropathological Correlates of Dementia.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2026Article
- Computer-aided Drug Design for Alzheimer's Disease: Recent Advancements and Future Perspectives.Current topics in medicinal chemistry · 2026Review
- The impact of anticholinergic burden on the development of mild behavioral impairment.medRxiv : the preprint server for health sciences · 2025Article
- Identifying synergistic combinations of repurposed treatments for Alzheimer's Disease.The journal of prevention of Alzheimer's disease · 2025Article
123 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Aggregation of amyloid-β (Aβ) as toxic oligomers and amyloid plaques within the brain appears to be the pathogenic event that initiates Alzheimer's disease (AD) lesions. One therapeutic strategy has been to reduce Aβ levels to limit its accumulation. Activation of certain neurotransmitter receptors can regulate Aβ metabolism. We assessed the ability of serotonin signaling to alter brain Aβ levels and plaques in a mouse model of AD and in humans. In mice, brain interstitial fluid (ISF) Aβ levels were decreased by 25% following administration of several selective serotonin reuptake inhibitor (SSRI) antidepressant drugs. Similarly, direct infusion of serotonin into the hippocampus reduced ISF Aβ levels. Serotonin-dependent reductions in Aβ were reversed if mice were pretreated with inhibitors of the extracellular regulated kinase (ERK) signaling cascade. Chronic treatment with an SSRI, citalopram, caused a 50% reduction in brain plaque load in mice. To test whether serotonin signaling could impact Aβ plaques in humans, we retrospectively compared brain amyloid load in cognitively normal elderly participants who were exposed to antidepressant drugs within the past 5 y to participants who were not. Antidepressant-treated participants had significantly less amyloid load as quantified by positron emission tomography (PET) imaging with Pittsburgh Compound B (PIB). Cumulative time of antidepressant use within the 5-y period preceding the scan correlated with less plaque load. These data suggest that serotonin signaling was associated with less Aβ accumulation in cognitively normal individuals.
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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.