Evidence map›Paper›PMID 21531375›Full record

ArticleThe American journal of pathology2011

Inflammation induced by infection potentiates tau pathological features in transgenic mice.

Michael Sy, Masashi Kitazawa, Rodrigo Medeiros, Lucia Whitman, David Cheng, Thomas E Lane, Frank M Laferla

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The American journal of pathology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

129 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  19. The endotoxin hypothesis of Alzheimer's disease.Molecular neurodegeneration · 2024
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69 more citing papers are in PubMed but not listed here.

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

7 authors.

Michael SyInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, California, USA.
Masashi Kitazawa
Rodrigo Medeiros
Lucia Whitman
David Cheng
Thomas E Lane
Frank M Laferla

Funding

UC Irvine Alzheimer's Disease Research Center Induced Pluripotent Stem Cell CoreP50AG016573 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 2000 to 2019
$37.0M
TISSUE REPOSITORY COREP01AG000538 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI GLABE, CHARLES G. · 1985 to 2018
$24.8M
Gene Interactions in a Model of Alzheimer's DiseaseR01AG021982 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 2003 to 2012
$3.3M
Modulating IBM pathology in transgenic miceR01AG020335 · NIA · UNIVERSITY OF CALIFORNIA IRVINE · PI LAFERLA, FRANK M · 2002 to 2005
$1.5M
Pathogenic Role of Abeta, tau and Inflammation in Inclusion Body MyositisK99AR054695 · NIAMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI KITAZAWA, MASASHI · 2007 to 2008
$165k
NIAMS NIH HHS K99AR054695NIA NIH HHS AG00538NIA NIH HHS P01 AG000538NIA NIH HHS P50 AG016573NIA NIH HHS P50AG16573NIA NIH HHS R01 AG020335NIA NIH HHS R01 AG021982NIA NIH HHS R01AG20335
6 · The paper itself

Abstract

Comorbidities that promote the progression of Alzheimer's disease (AD) remain to be uncovered and evaluated in animal models. Because elderly individuals are vulnerable to viral and bacterial infections, these microbial agents may be considered important comorbidities that could potentiate an already existing and tenuous inflammatory condition in the brain, accelerating cognitive decline, particularly if the cellular and molecular mechanisms can be defined. Researchers have recently demonstrated that triggering inflammation in the brain exacerbates tau pathological characteristics in animal models. Herein, we explore whether inflammation induced via viral infection, compared with inflammation induced via bacterial lipopolysaccharide, modulates AD-like pathological features in the 3xTg-AD mouse model and provide evidence to support the hypothesis that infectious agents may act as a comorbidity for AD. Our study shows that infection-induced acute or chronic inflammation significantly exacerbates tau pathological characteristics, with chronic inflammation leading to impairments in spatial memory. Tau phosphorylation was increased via a glycogen synthase kinase-3β-dependent mechanism, and there was a prominent shift of tau from the detergent-soluble to the detergent-insoluble fraction. During chronic inflammation, we found that inhibiting glycogen synthase kinase-3β activity with lithium reduced tau phosphorylation and the accumulation of insoluble tau and reversed memory impairments. Taken together, infectious agents that trigger central nervous system inflammation may serve as a comorbidity for AD, leading to cognitive impairments by a mechanism that involves exacerbation of tau pathological characteristics.

Indexed as

AgingAlzheimer DiseaseAmyloid beta-PeptidesAnimalsCognitionCytokinesGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaInflammationInjectionsLipopolysaccharidesLithiumMemoryMiceMice, TransgenicMurine hepatitis virusAmyloid beta-PeptidesCytokinesGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaGsk3b protein, mouseLipopolysaccharidesLithiumtau Proteins

Identifiers

PMID21531375
PMCPMC3124234

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.