The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index; 15 of the 49 sources its claims cite were checked for support.
An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice
Open accessAbstract
The antidepressant drug citalopram decreased CSF amyloid-β in healthy humans, and in an aged transgenic mouse model of Alzheimer’s disease, it decreased ISF amyloid-β in a dose-dependent manner.
Overview
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Written from the paper’s full text.
TL;DR
In aged APP/PS1 mice, citalopram dose-dependently lowered brain interstitial fluid Aβ, blocked growth of existing plaques, and reduced new plaque appearance by 78%. In healthy human volunteers, acute citalopram reduced CSF Aβ production by 37% and total CSF Aβ concentrations by 38% without changing clearance.
Key findings
- In 12-month-old plaque-bearing APP/PS1 mice, citalopram reduced ISF Aβ at 5 mg/kg (12.4%) and 10 mg/kg (24.5%) versus baseline; 20 mg/kg gave no additional effect (27.5% reduction), while 2.5 mg/kg was not significant.
- Chronic citalopram (10 mg/kg daily for 28 days) prevented plaque growth: vehicle plaques grew 111.4 μm² on average, whereas citalopram plaques did not grow (−22.4 μm², p=0.26); new plaques were reduced from 10 (3.9) to 2.2 (1.1), p=0.01, a 78% reduction.
- In healthy human volunteers, citalopram lowered mean CSF Aβ production rate to 1.33 pg/hr (0.15) versus 2.11 pg/hr (0.20) for placebo, a 37% reduction (p=0.005), and lowered average CSF Aβ concentration by 38% over 37 hours (p=0.001).
- Aβ clearance rate was unchanged (−0.61 versus −0.96 per hour; p=0.115), and tracer/tracee ratio did not differ significantly between groups.
Methods
- Mouse studies used APP/PS1+/− mice: in vivo hippocampal microdialysis to measure ISF Aβ after acute citalopram doses (2.5, 5, 10, 20 mg/kg) and longitudinal multiphoton microscopy with thinned-skull cranial windows to track individual plaque growth over 28 days of citalopram (10 mg/kg) or vehicle.
- Human study was a randomized, double-blind, placebo-controlled trial in healthy volunteers receiving 60 mg citalopram in divided oral doses; CSF and blood were sampled hourly during stable-isotope labeling kinetics (SILK) with 13C6-leucine, and labeled/unlabeled Aβ was measured by mass spectrometry.
- Analyses used repeated-measures ANOVA with treatment, time, and treatment-by-time effects, mixed models, post-hoc approximate t-tests, and non-proportional odds cumulative logit models for plaque outcomes.
Limitations
- The paper states that human data were not collected during the first 8 hours after drug/placebo administration, so the timing of when CSF concentration differences arose is unknown.
- The paper states that human studies were conducted in young individuals presumably before plaque formation, so it is unknown whether the same effect occurs in older individuals with plaque deposition.
- The paper notes that production and clearance were modeled as independent phenomena even though they occur simultaneously; evident additional constraints include the small human sample (23 analyzed), acute dosing rather than long-term prevention outcomes, and adverse events including post-lumbar puncture headaches and nausea/vomiting.
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Claims the paper makes
24 Own result · 13 Own method · 13 Own interpretation · 10 Not checked yet · 8 No full text of the sources · 5 Supported · 3 Supported so far · 1 Partly supported · 1 Mixed support · 1 Not supported · 1 No basis given · accuracy not yet measured
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“Serotonin signaling suppresses generation of amyloid-β (Aβ) in vitro and in animal models of Alzheimer’s disease (AD).”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Abstract
What the sources say
- Not checked — no full text of the sourcecites [10] Arjona AA Pooler AM Lee RK Wurtman RJ Effect of a 5-HT(2C) serotonin agonist, dexnorfenfluramine, on amyloid precursor protein metabolism in guinea pigs Brain Res 951 135 9 27 2002 12231467 source
- Partly supportedcites [11] Nitsch RM Deng M Growdon JH Wurtman RJ Serotonin 5-HT2a and 5-HT2c receptors stimulate amyloid precursor protein ectodomain secretion J Biol Chem 271 4188 2 23 1996 8626761 sourceExperimental — accuracy not yet measured
The Discussion (page not provided) reports that serotonin increased non-amyloidogenic APP ectodomain secretion in cultured cells, which could reduce amyloidogenic products. But the authors say they could not measure Aβ in those experiments and that an effect on Aβ secretion remained to be investigated. The cited paper also does not report experiments in animal models of AD. (LLM, conf=0.87)
- Disputedcites [12] Robert SJ Zugaza JL Fischmeister R Gardier AM Lezoualc’h F The human serotonin 5-HT4 receptor regulates secretion of non-amyloidogenic precursor protein J Biol Chem 276 44881 11 30 2001 11584021 sourceExperimental — accuracy not yet measured
In “Effect of 5-HT4 Receptor Activation on Aβ Production,” the authors report no effect of serotonin on Aβ production in CHO cells compared with untreated controls, contrary to the claimed in vitro suppression. The provided passages do not report Aβ suppression in animal models of AD. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
- Supportedcites [13] Cirrito JR Serotonin signaling is associated with lower amyloid-beta levels and plaques in transgenic mice and humans Proc Natl Acad Sci U S A 108 14968 9 6 2011 21873225 PMC3169155 source
The introductory passage (section labelled Abstract; page unavailable) reports that activation of select serotonin receptors increases nonamyloidogenic APP processing in vitro, which prevents Aβ formation. The Abstract and Results report reduced Aβ production following serotonin signaling in mouse models of AD. The in vitro finding is reported from earlier studies, not presented as this paper’s own experiment. (LLM, conf=0.90)
- Partly supportedcites [14] Nelson RL Prophylactic treatment with paroxetine ameliorates behavioral deficits and retards the development of amyloid and tau pathologies in 3xTgAD mice Exp Neurol 205 166 5 2007 17368447 PMC1979096 sourceExperimental — accuracy not yet measured
The Results (page not provided) show that paroxetine treatment lowered Aβ1−40 levels in 3xTgAD mice, but did not significantly affect Aβ1−42. The Discussion says serotonergic signaling might mediate this effect, while also allowing a mechanism independent of serotonin signaling. The paper does not establish that serotonin signaling suppresses Aβ generation, and it reports no in vitro experiment of its own. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Activation of serotonin receptors has been shown to reduce Aβ production in vitro; treatment with serotonin or receptor agonists activates intracellular signaling cascades and increases levels of the α-secretase product sAPP-α (10–12).”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Introduction
What the sources say
- Not checked — no full text of the sourcecites [10] Arjona AA Pooler AM Lee RK Wurtman RJ Effect of a 5-HT(2C) serotonin agonist, dexnorfenfluramine, on amyloid precursor protein metabolism in guinea pigs Brain Res 951 135 9 27 2002 12231467 source
- Disputedcites [11] Nitsch RM Deng M Growdon JH Wurtman RJ Serotonin 5-HT2a and 5-HT2c receptors stimulate amyloid precursor protein ectodomain secretion J Biol Chem 271 4188 2 23 1996 8626761 sourceExperimental — accuracy not yet measured
The Discussion says the authors could not measure Aβ secretion in the serotonin-treated 3T3 cells and that whether serotonin receptor stimulation changes Aβ secretion remains to be investigated. The Results show increased APPs secretion, but not the claimed reduction in Aβ production. (LLM, conf=0.86)
Checked by a reasoning model — may be wrong.
- Disputedcites [12] Robert SJ Zugaza JL Fischmeister R Gardier AM Lezoualc’h F The human serotonin 5-HT4 receptor regulates secretion of non-amyloidogenic precursor protein J Biol Chem 276 44881 11 30 2001 11584021 sourceExperimental — accuracy not yet measured
In “Effect of 5-HT4 Receptor Activation on Aβ Production” (page not supplied), the authors report no effect of serotonin on Aβ production in their CHO-cell experiment. The Discussion likewise says that receptor stimulation did not change secreted Aβ levels, although it increased sAPPα secretion. (LLM, conf=0.93)
Checked by a reasoning model — may be wrong.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Modulating serotonin levels in vivo shows consistent effects: single-dose treatment of SSRIs in young APP/PS1 mice reduced Aβ levels in the brain interstitial fluid (ISF) by 25% (13).”
- Also stated in: § Citalopram dose-response in aged APP/PS1 mice · boosted
“Previous studies demonstrated in 3 month old APP/PS1+/− mice, an age prior to Aβ pathology, that 10mg/kg citalopram reduces brain ISF Aβ concentrations by 25% (13).”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Introduction
What the sources say
- Supportedcites [13] Cirrito JR Serotonin signaling is associated with lower amyloid-beta levels and plaques in transgenic mice and humans Proc Natl Acad Sci U S A 108 14968 9 6 2011 21873225 PMC3169155 source
The Results report that a single administration of several SSRIs to 2- to 3-month-old PS1APP mice reduced brain ISF Aβ, with levels remaining 25% lower at 24 hours. The Discussion also summarizes acute SSRI treatment as reducing ISF Aβ by 25%. (LLM, conf=0.94)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Citalopram dose-response in aged APP/PS1 mice · boosted
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In animal models, a 12–25% reduction in Aβ concentrations was sufficient to dramatically decrease plaque formation (32).”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Discussion
What the sources say
- Partly supportedcites [32] Yan P Characterizing the appearance and growth of amyloid plaques in APP/PS1 mice J Neurosci 29 10706 8 26 2009 19710322 PMC2756291 sourceExperimental — accuracy not yet measured
The Results report that Compound E dramatically attenuated new plaque appearance in APP/PS1 mice, while a separate Results passage reports 24-hour reductions of 22% and 25% in interstitial-fluid Aβ. Our copy does not report a 12% reduction, and the Discussion describes the reduction in Aβ as associated with—not definitively sufficient to cause—the reduction in plaque formation. No page numbers are available in our copy. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Chronic SSRI treatment over the course of four months reduced Aβ plaque load by 50% in mice (13).”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Introduction
What the sources say
- Supportedcites [13] Cirrito JR Serotonin signaling is associated with lower amyloid-beta levels and plaques in transgenic mice and humans Proc Natl Acad Sci U S A 108 14968 9 6 2011 21873225 PMC3169155 source
The Results report that PS1APP mice received the SSRI citalopram for four months and had significantly less plaque burden than water-treated controls. Hippocampal plaque load fell by 50% (and cortical plaque load by 62%), supporting the citing sentence's 50% figure. (LLM, conf=0.95)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“In humans, CSF Aβ concentrations begin changing before tau levels; amyloid deposition occurs in the brain decades before the onset of clinical symptoms (3–5).”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Introduction
What the sources say
- Not checked — no full text of the sourcecites [3] Price JL Morris JC Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease Ann Neurol 45 358 3 1999 10072051 source
- Not checked — no full text of the sourcecites [4] Hardy J Selkoe DJ The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics Science 297 353 7 19 2002 12130773 source
- Supportedcites [5] Bateman RJ Clinical and Biomarker Changes in Dominantly Inherited Alzheimer’s Disease N Engl J Med 7 11 2012 PMC3474597 22784036 source
The Results (Combined Model) report that CSF Aβ42 appeared to decline about 25 years before expected symptom onset in human mutation carriers, while CSF tau increases were detected about 15 years before onset. This supports the attributed ordering of the changes. (LLM, conf=0.93)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Stimulation of serotonin receptors activates the ERK signaling cascade in as little as 5 minutes (27–29).”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Discussion
What the sources say
- Not checked — no full text of the sourcecites [27] Lione A Errico M Lin S Cowen D Activation of extracellular signal-regulated kinase (ERK) and Akt by human serotonin 5-HT1B receptors in transfected BE(2)-C neuroblastoma cells is inhibited by RGS4 J Neurochem 2000 9 75 3 934 8 10936173 source
- Supportedcites [28] Johnson-Farley N Kertesy S Dubyak G Cowen D Enhanced activation of Akt and extracellular-regulated kinase pathways by simultaneous occupancy of Gq-coupled 5-HT2A receptors and Gs-coupled 5-HT7A receptors in PC12 cells J Neurochem 2005 1 92 1 72 82 15606897 source
The figure captions reproduced in the Discussion (Figs. 2–3) describe ERK activation after five-minute treatments with 5-HT or a serotonin-receptor agonist in PC12 cells. This supports the stated timing in the cell models studied. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [29] Norum J Hart K Levy F Ras-dependent ERK activation by the human Gs-coupled serotonin receptors 5-HT4(b) and 5-HT7(a) J Biol Chem 2003 1 31 278 5 3098 104 12446729 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Every source the paper cites for this claim was checked and supports it.
In the paper
“In those studies, serotonin signaling did not alter the rate of Aβ clearance, suggesting that reduced Aβ production was responsible for lower Aβ concentrations.”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Introduction
What the sources say
- Supportedcites [13] Cirrito JR Serotonin signaling is associated with lower amyloid-beta levels and plaques in transgenic mice and humans Proc Natl Acad Sci U S A 108 14968 9 6 2011 21873225 PMC3169155 source
In the Results section, serotonin-treated and vehicle-treated mice had the same ISF Aβ elimination half-life, approximately one hour. The authors conclude that altered elimination did not explain the lower Aβ levels and report reduced Aβ production instead. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Our previous studies demonstrated that ERK activation was required for serotonin-dependent suppression of Aβ (13).”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Discussion
What the sources say
- Supportedcites [13] Cirrito JR Serotonin signaling is associated with lower amyloid-beta levels and plaques in transgenic mice and humans Proc Natl Acad Sci U S A 108 14968 9 6 2011 21873225 PMC3169155 source
The Results section, under “ERK Is Required for Serotonin-Dependent Depression of ISF Aβ,” reports that inhibiting MEK or ERK completely blocked citalopram’s effect on interstitial-fluid Aβ levels in mice. The Discussion likewise states that the ERK cascade is required for serotonin-receptor-mediated changes in Aβ generation. (LLM, conf=0.94)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“SSRI treatment in the 3xTg AD mouse model showed similar reductions in Aβ (14).”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Introduction
What the sources say
- Supportedcites [14] Nelson RL Prophylactic treatment with paroxetine ameliorates behavioral deficits and retards the development of amyloid and tau pathologies in 3xTgAD mice Exp Neurol 205 166 5 2007 17368447 PMC1979096 source
The Results report that paroxetine-treated 3xTgAD mice had significantly lower cortical Aβ1−40 levels than saline-treated mice, with reductions exceeding 50% in both sexes. They also report fewer hippocampal neurons with Aβ accumulations. Paroxetine is the SSRI treatment described in the claim. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
- Probably not a substantial claim. 21
- It may state two separate claims as one. 11
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Nonetheless, the efficacy of the current proposed prevention strategy depends critically on the validity of the amyloid hypothesis of Alzheimer’s disease.”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Discussion
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“Citalopram is one of the most selective SSRIs for serotonin re-uptake and has among the most favorable side effect profiles compared with other antidepressants (17).”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Results > Citalopram dose-response in aged APP/PS1 mice
What the sources say
- Not checked yetcites [17] Cipriani A Furukawa T Salanti G Geddes J Higgins J Churchill R Watanabe N Nakagawa A Omori I McGuire H Tansella M Barbui C Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis Lancet 373 746 758 2009 19185342
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Current theories for SSRI- mediated treatment of depression include increased production of BDNF (22), increased hippocampal neurogenesis (23–25) and reduced expression of serotonin autoreceptors (26).”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Discussion
What the sources say
- Not checked yetcites [22] Sen S Duman R Sanacora G Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications Biol Psychiatry 2008 9 15 64 6 527 32 18571629 PMC2597158
- Not checked yetcites [23] Malberg J Eisch A Nestler E Duman R Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus J Neurosci 2000 12 15 20 24 9104 10 11124987 PMC6773038
- Not checked yetcites [24] Kempermann G Kronenberg G Depressed new neurons--adult hippocampal neurogenesis and a cellular plasticity hypothesis of major depression Biol Psychiatry 2003 9 1 54 5 499 503 12946878
- Not checked yetcites [25] Eisch AJ Petrik D Depression and hippocampal neurogenesis: a road to remission? Science 2012 10 5 338 72 5 23042885 PMC3756889
- Not checked yetcites [26] Hamon M Blier P Monoamine neurocircuitry in depression and strategies for new treatments Prog Neuropsychopharmacol Biol Psychiatry 2013 8 1 45 54 63 23602950
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For newly generated Aβ, the power of time by treatment group interaction was also > 99.99% while the power of the main effect of treatment was 66.18%.”
- Also stated in: § Study Design · plain
“For newly generated Aβ, the power of time by treatment group interaction was also > 99.99% while the power of the main effect of treatment was 66.18%.”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Materials and Methods > Study Design
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Also stated in: § Study Design · plain
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In order to account for the within-subject dependencies in the outcome variables, these models incorporated a random intercept at the subject level and, for plaque growth, also a random intercept at the plaque level.”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Materials and Methods > Study Design
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The concentrations over the time course were such that steady-state kinetics applied reasonably well after the first 12 hours and the rate of change of concentration appeared similar in both groups.”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Discussion
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Based on the power analysis of the data, for Aβ concentration with alpha=0.05, the power of the time by treatment group interaction was > 99.99% and the power of the main effect of treatment was 95.03%.”
- Also stated in: § Study Design · plain
“Based on a repeated measures ANOVA, with a compound symmetry covariance structure and alpha=0.05, for Aβ concentration the power of the time by treatment group interaction was > 99.99% and the power of the main effect of treatment was 95.03%.”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Materials and Methods > Study Design
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Also stated in: § Study Design · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, the tracer/tracee ratio (labeled Aβ/unlabeled Aβ) (TTR) over the 37 hours of CSF sampling was overlapping for both groups (Fig. S2 suggesting that the fractional turnover of Aβ was unchanged at the time of the SILK study and that Aβ metabolism had reached a new steady state.”
- Also stated in: § Discussion · hedged
“Tracer kinetics established that the fractional turnover rate in the two groups was very similar suggesting that Aβ metabolism had reached a new steady state at the time when the SILK study was carried out.”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Results > Citalopram reduces CSF Aβ production and concentrations in humans
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Discussion · hedged
None of the sources cited for this claim have been checked yet.
In the paper
“In humans, CSF Aβ concentrations begin changing before tau levels; amyloid deposition occurs in the brain decades before the onset of clinical symptoms (3–5).”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Introduction
What the sources say
- Not checked yetcites [3] Price JL Morris JC Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease Ann Neurol 45 358 3 1999 10072051
- Not checked yetcites [4] Hardy J Selkoe DJ The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics Science 297 353 7 19 2002 12130773
- Not checked yetcites [5] Bateman RJ Clinical and Biomarker Changes in Dominantly Inherited Alzheimer’s Disease N Engl J Med 7 11 2012 PMC3474597 22784036
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A randomized double-blind placebo controlled study was performed to determine the central nervous system effect of 60 mg of the SSRI antidepressant citalopram, given in divided oral doses (2 doses of 30 mg each).”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Materials and Methods > Study Design
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data suggest that citalopram reduced CSF Aβ concentrations by suppressing Aβ production while having a negligible effect on Aβ clearance mechanisms.”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Results > Citalopram reduces CSF Aβ production and concentrations in humans
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For newly generated Aβ, the power of time by treatment group interaction was also > 99.99% while the power of the main effect of treatment was 66.18%.”
- Also stated in: § Study Design · plain
“For newly generated Aβ, the power of time by treatment group interaction was also > 99.99% while the power of the main effect of treatment was 66.18%.”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Materials and Methods > Study Design
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Also stated in: § Study Design · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Phosphorylation of either of these secretase enzymes by activated ERK could occur within minutes of SSRI treatment, thus accounting for the rapid changes in Aβ levels.”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, these results suggest that citalopram reduces plaque appearance and growth, but has no effect on plaque regression.”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Results > Chronic citalopram treatment blocks plaque-growth in APP/PS1 mice
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The models also incorporated a Toeplitz covariance structure for the model errors in basal ISF Aβ, first-order autoregressive process heterogeneous variance covariance structure for the model errors in newly-generated Aβ and the same covariance structure but with homogeneous variance for CSF concentrations of total Aβ and TTR, as these provided the best measures on Akaike’s information criterion (”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Materials and Methods > Study Design
What the sources say
- Not checked yetcites [39] Akaike H A new look at the statistical model identification IEEE Transactions on Automatic Control 19 716 1974
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“After citalopram treatment in mice, we also found increased α-secretase activity, which appears to be downstream of ERK signaling (30).”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Discussion
What the sources say
- Not checked yetcites [30] Cisse M Duplan E Guillot-Sestier MV Rumigny J Bauer C Pages G Orzechowski HD Slack B Checler F Vincent B The extracellular regulated kinase-1 (ERK1) controls regulated alpha-secretase-mediated processing, promoter transactivation, and mRNA levels of the cellular prion protein J Biol Chem 2011 8 19 286 33 29192 206 21586567 PMC3190726
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Another limitation is that our human studies were conducted in young individuals, presumably prior to plaque formation.”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Discussion
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Citalopram is one of the most selective SSRIs for serotonin re-uptake and has among the most favorable side effect profiles compared with other antidepressants (17).”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Results > Citalopram dose-response in aged APP/PS1 mice
What the sources say
- Not checked yetcites [17] Cipriani A Furukawa T Salanti G Geddes J Higgins J Churchill R Watanabe N Nakagawa A Omori I McGuire H Tansella M Barbui C Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis Lancet 373 746 758 2009 19185342
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Serotonin receptor levels are reduced in human AD brains (8,9).”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Introduction
What the sources say
- Not checked yetcites [8] Arai H Kosaka K Iizuka R Changes of biogenic amines and their metabolites in postmortem brains from patients with Alzheimer-type dementia J Neurochem 43 388 8 1984 6204013
- Not checked yetcites [9] Reynolds GP 5-Hydroxytryptamine (5-HT)4 receptors in post mortem human brain tissue: distribution, pharmacology and effects of neurodegenerative diseases British journal of pharmacology 114 993 3 1995 7780656 PMC1510307
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Admittedly, this model is limited by presuming that production and clearance rates are independent phenomena in the analysis, while practically production and clearance occur simultaneously.”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Materials and Methods > Study Design
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- The authors state this as an assumption: The model presumes that production and clearance rates are independent phenomena in the analysis.
In the paper
“The accumulation of amyloid-β (Aβ) peptide in the brain and its aggregation into amyloid plaques is currently considered the pathological trigger for AD (2).”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Introduction
What the sources say
- Not checked yetcites [2] Holtzman DM Morris JC Goate AM Alzheimer’s disease: the challenge of the second century Science translational medicine 3 77sr1 4 6 2011 21471435 PMC3130546
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Placebo and citalopram treated volunteers were first matched on gender and then as closely as possible in age, always within 5 years.”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Results > Citalopram reduces CSF Aβ production and concentrations in humans
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Importantly, this effect was seen in the production phase of Aβ with no significant group differences initially, but with subsequent differences that remained throughout the production phase and with no effect on clearance.”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, since the groups were not explicitly matched on race, at study mid-point the groups were checked by an unblinded research assistant to ensure that they were balanced in racial composition.”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Results > Citalopram reduces CSF Aβ production and concentrations in humans
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Based on the power analysis of the data, for Aβ concentration with alpha=0.05, the power of the time by treatment group interaction was > 99.99% and the power of the main effect of treatment was 95.03%.”
- Also stated in: § Study Design · plain
“Based on a repeated measures ANOVA, with a compound symmetry covariance structure and alpha=0.05, for Aβ concentration the power of the time by treatment group interaction was > 99.99% and the power of the main effect of treatment was 95.03%.”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Materials and Methods > Study Design
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Also stated in: § Study Design · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, these trials were conducted after the onset of clinical symptoms and thus may have been too late to prevent further disease progression.”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Rests on an assumption: There have been many clinical trials using Aβ lowering drugs in AD and MCI that were unsuccessful.
None of the sources cited for this claim have been checked yet.
In the paper
“Activation of serotonin receptors has been shown to reduce Aβ production in vitro; treatment with serotonin or receptor agonists activates intracellular signaling cascades and increases levels of the α-secretase product sAPP-α (10–12).”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Introduction
What the sources say
- Not checked yetcites [10] Arjona AA Pooler AM Lee RK Wurtman RJ Effect of a 5-HT(2C) serotonin agonist, dexnorfenfluramine, on amyloid precursor protein metabolism in guinea pigs Brain Res 951 135 9 27 2002 12231467
- Not checked yetcites [11] Nitsch RM Deng M Growdon JH Wurtman RJ Serotonin 5-HT2a and 5-HT2c receptors stimulate amyloid precursor protein ectodomain secretion J Biol Chem 271 4188 2 23 1996 8626761
- Not checked yetcites [12] Robert SJ Zugaza JL Fischmeister R Gardier AM Lezoualc’h F The human serotonin 5-HT4 receptor regulates secretion of non-amyloidogenic precursor protein J Biol Chem 276 44881 11 30 2001 11584021
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A limitation of the study is that data were not collected during the eight hours following drug/placebo administration.”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
To date, there have not been drugs with both an established safety profile and a mechanism-based rationale that have been tested in primary or secondary prevention trials of AD.
“To date, there have not been drugs with both an established safety profile and a mechanism-based rationale that have been tested in primary or secondary prevention trials of AD.”
The paper relies on this without support.
Early in disease pathogenesis, soluble Aβ monomers aggregate into soluble Aβ oligomers and insoluble Aβ plaques, both of which can alter synaptic transmission and be toxic to neurons under certain conditions.
“Early in disease pathogenesis, soluble Aβ monomers aggregate into soluble Aβ oligomers and insoluble Aβ plaques, both of which can alter synaptic transmission and be toxic to neurons under certain conditions.”
The paper relies on this without support.
Individuals with autosomal dominant AD or Down’s syndrome have only 20–50% higher CSF Aβ42 concentrations than normal but manifest disease 20–30 years before AD patients with the sporadic form of the disease.
“Individuals with autosomal dominant AD or Down’s syndrome have only 20–50% higher CSF Aβ42 concentrations than normal but manifest disease 20–30 years before AD patients with the sporadic form of the disease.”
The paper relies on this without support.
There have been many clinical trials using Aβ lowering drugs in AD and MCI that were unsuccessful.
“A caveat is that there have been many clinical trials using Aβ lowering drugs in AD and MCI that were unsuccessful.”
The paper relies on this without support.
Citalopram has a long half-life.
“Citalopram has a long half-life, meaning there was likely a sustained effect on Aβ throughout CSF sampling despite the single administration at the beginning of the study.”
The authors state this as an assumption.
The model presumes that production and clearance rates are independent phenomena in the analysis.
“Admittedly, this model is limited by presuming that production and clearance rates are independent phenomena in the analysis, while practically production and clearance occur simultaneously.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Sheline et al. proposed that Citalopram, an SSRI, decreased cerebrospinal fluid (CSF) amyloid beta protein production in a dose-dependent manner in both animal and human studies”
From Risk analysis of use of different classes of antidepressants on subsequent dementia: A nationwide cohort study in Taiwan (2017) · cites this paper as [56]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“and this ability may be a potential preventive strategy for AD [56].”
From Risk analysis of use of different classes of antidepressants on subsequent dementia: A nationwide cohort study in Taiwan (2017) · cites this paper as [56]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Results > Citalopram reduces CSF Aβ production and concentrations in humans
“Healthy subjects age 18–50, without medical disease, electrocardiogram (ECG) or laboratory abnormalities and with no prior history of antidepressant treatment, were enrolled in a double-blind study.”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Materials and Methods > Study Design
“Healthy 21–50 year old male and female volunteers were invited to participate, screened, and enrolled.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Materials and Methods > Study Design
“This technique samples soluble molecules within the extracellular fluid that are smaller than 38-kilodaltons, the molecular-weight cut off of the probe membrane.”
§ An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice > Materials and Methods > Study Design
“Two millimeter microdialysis probes were inserted through the guides so the membrane was contained entirely within the hippocampus (BR-2, 30-kilodalton MWCO membrane, Bioanalytical Systems).”
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Sorted by citations
Dementia prevention, intervention, and care
Livingston, G., Sommerlad, A., Orgeta, V., Costafreda, S. G., Huntley, J., Ames, D., Ballard, C., Banerjee, S., Burns, A., Cohen-Mansfield, J., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31363-6 · Cited by 6,072
The Epidemiology of Alzheimer's Disease Modifiable Risk Factors and Prevention
Zhang, X.-X., Tian, Y., Wang, Z.-T., Ma, Y.-H., Tan, L., & Yu, J.-T. (2021) · The Journal of Prevention of Alzheimer's Disease · doi:10.14283/jpad.2021.15 · Cited by 789
Considering sex and gender in Alzheimer disease and other dementias
Podcasy, J., & Epperson, C. N. (2016) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2016.18.4/cepperson · Cited by 727
Mechanisms and treatment of late-life depression
Alexopoulos, G. S. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0514-6 · Cited by 592
Depression—an underrecognized target for prevention of dementia in Alzheimer’s disease
Dafsari, F. S., & Jessen, F. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0839-1 · Cited by 312
Metadata
- Authors
- Sheline, Y. I., West, T., Yarasheski, K., Swarm, R., Jasielec, M. S., Fisher, J. R., Ficker, W. D., Yan, P., Xiong, C., Frederiksen, C., Grzelak, M. V., Chott, R., Bateman, R. J., Morris, J. C., Mintun, M. A., Lee, J.-M., & Cirrito, J. R.
- Affiliations
- University of Pennsylvania (US)
- C2N Diagnostics (United States) (US)
- Washington University in St. Louis (US)
- Avid Radiopharmaceuticals (United States) (US)
- Corresponding author
- Sheline, Yvette I.
- ORCID
- Venue
- Science Translational Medicine
- Published
- 2014-05-14
- Volume
- 6
- Issue
- 236
- Pages
- 236re4-236re4
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC4269372
- OpenAlex
- W2163894029
- Semantic Scholar
- 60d1eff17ddf2e7b53b76651fafa944ed8ffb4f3
- Cited by
- 223
- References
- 43
- Citations by year
- 2026: 8 · 2025: 18 · 2024: 19 · 2023: 11 · 2022: 19 · 2021: 17 · 2020: 21 · 2019: 14 · 2018: 24 · 2017: 17 · 2016: 18 · 2015: 24 · 2014: 12
- FWCI
- 8.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5p60dk020579-35)
- National Institute on Aging (R01AG042513, R01AG041502, R21AG039690)
- National Institute of Mental Health (K24MH079510)
- National Institute of General Medical Sciences (R24GM136766, P41GM103422)
- National Institute of Diabetes and Digestive and Kidney Diseases (P60-DK-020579, P30DK056341, P30DK020579)
- National Institute of Neurological Disorders and Stroke (R21NS082529, R01NS067905)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Keywords
- citalopram, serotonin signaling, amyloid-beta, Alzheimer's disease, cerebrospinal fluid, amyloid plaques, APP/PS1 mice, selective serotonin reuptake inhibitors, amyloid-beta production, drug-target engagement, Alzheimer's disease prevention
- MeSH terms
- Adult, Alzheimer Disease, Animals, Antidepressive Agents, Brain, Dose-Response Relationship, Drug, Double-Blind Method, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Mice, Inbred C3H, Mice, Transgenic, Middle Aged, Prospective Studies, Serotonin, Citalopram, Signal Transduction, Amyloid beta-Protein Precursor, Selective Serotonin Reuptake Inhibitors, Microdialysis, Mice, Young Adult, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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