Evidence map›Paper›PMID 33775832›Full record

ArticleBrain, behavior, and immunity2021

Inflammation, negative affect, and amyloid burden in Alzheimer's disease: Insights from the kynurenine pathway.

Auriel A Willette, Colleen Pappas, Nathan Hoth, Qian Wang, Brandon Klinedinst, Sara A Willette, Brittany Larsen, Amy Pollpeter, Tianqi Li, Scott Le and 5 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain, behavior, and immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 3 pooled it
2.8field-weighted citation impact, top 8% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 3 syntheses or guidelines pooled it, 57 citations in OpenAlex.

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  9. The spleen-brain axis in Alzheimer's disease and related dementias: Integrating immune and metabolic regulation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Auriel A WilletteDepartment of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA; Neuroscience Graduate Program, Iowa State University, Ames, IA, USA; Department of Psychology, Iowa State University, Ames, IA, USA; Department of Neurology, University of Iowa, Iowa City, IA, USA; Bioinformatics and Computational Biology Graduate Program, Iowa State University, Ames, IA, USA; Department of Biomedical Sciences, Iowa State University, Ames, IA, USA. Electronic address: awillett@iastate.edu.
Colleen PappasDepartment of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA.
Nathan HothDepartment of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA.
Qian WangDepartment of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA.
Brandon KlinedinstNeuroscience Graduate Program, Iowa State University, Ames, IA, USA.
Sara A WilletteDepartment of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA.
Brittany LarsenNeuroscience Graduate Program, Iowa State University, Ames, IA, USA.
Amy PollpeterBioinformatics and Computational Biology Graduate Program, Iowa State University, Ames, IA, USA.
Tianqi LiBioinformatics and Computational Biology Graduate Program, Iowa State University, Ames, IA, USA.
Scott LeDepartment of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA.
Ana D Collazo-MartinezDepartment of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA.
Jonathan P MochelDepartment of Biomedical Sciences, Iowa State University, Ames, IA, USA.
Karin AllenspachDepartment of Veterinary Clinical Sciences, Iowa State University, Ames, IA, USA.
Robert DantzerDepartment of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Alzheimer's Disease Neuroimaging Initiative
Iowa State University · USThe University of Texas MD Anderson Cancer Center · USUniversity of Iowa · US

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
Insulin Resistance, Biomarkers of Brain Function, and Intermittent Calorie RestrictionR00AG047282 · NIA · IOWA STATE UNIVERSITY · PI WILLETTE, AURIEL · 2016 to 2021
$730k
Insulin Resistance, Biomarkers of Brain Function, and Intermittent Calorie RestrictionK99AG047282 · NIA · IOWA STATE UNIVERSITY · PI WILLETTE, AURIEL · 2015 to 2015
$135k
NIA NIH HHS K99 AG047282NIA NIH HHS R00 AG047282NIA NIH HHS U01 AG024904
6 · The paper itself

Abstract

backgroundDepressive symptoms in Alzheimer's disease (AD) predict worse cognitive and functional outcomes. Both AD and major depression inflammatory processes are characterized by shunted tryptophan metabolism away from serotonin (5-HT) and toward the neuroinflammatory kynurenine (Kyn) pathway. The present study assessed associations between Kyn and behavioral, neuroanatomical, neuropathological, and physiological outcomes common to both AD and negative affect across the AD continuum.

methodsIn 58 cognitively normal, 396 mild cognitive impairment, and 112 AD participants from the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI1) cohort, serum markers of 5-HT, tryptophan, and Kyn were measured and their relationships investigated with immunologic markers, affect and functional outcomes, CSF markers of beta-amyloid (Aβ) and tau, and regional gray matter.

resultsA higher Kyn/Tryptophan ratio was linked to many inflammatory markers, as well as lower functional independence and memory scores. A higher Kyn/5-HT ratio showed similar associations, but also strong relationships with negative affect and neuropsychiatric disturbance, executive dysfunction, and global cognitive decline. Further, gray matter atrophy was seen in hippocampus, anterior cingulate, and prefrontal cortices, as well as greater amyloid and total tau deposition. Finally, using moderated-mediation, several pro-inflammatory factors partially mediated Kyn/5-HT and negative affect scores in participants with subclinical Aβ (i.e., Aβ-), whereas such associations were fully mediated by Complement 3 in Aβ+ participants.

conclusionThese findings suggest that inflammatory signaling cascades may occur during AD, which is associated with increased Kyn metabolism that influences the pathogenesis of negative affect. Aβ and the complement system may be critical contributing factors in this process.

Indexed as

Alzheimer DiseaseCognitive DysfunctionAmyloid beta-PeptidesHumansInflammationKynurenineAmyloid beta-PeptidesKynurenineAlzheimer’s diseaseDepressionInflammationKynurenineSerotoninTryptophan

Identifiers

PMID33775832
PMCPMC8187283
OpenAlexW3142533463

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.