Evidence map›Paper›PMID 24150111›Full record

ArticleJournal of Alzheimer's disease : JAD2014

Autoimmune manifestations in the 3xTg-AD model of Alzheimer's disease.

Monica Marchese, David Cowan, Elizabeth Head, Donglai Ma, Khalil Karimi, Vanessa Ashthorpe, Minesh Kapadia, Hui Zhao, Paulina Davis, Boris Sakic

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

Article in Journal of Alzheimer's disease : JAD, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

52 citing papers in PubMed, 102 citations in OpenAlex.

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  8. Rebalancing Immune Interactions within the Brain-Spleen Axis Mitigates Neuroinflammation in an Aging Mouse Model of Alzheimer's Disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025
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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

10 authors at 2 institutions in 2 countries.

Monica MarcheseDepartment of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
David CowanDepartment of Medicine, McMaster University, Hamilton, ON, Canada.
Elizabeth HeadDepartment of Molecular & Biomedical Pharmacology, Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
Donglai MaDepartment of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
Khalil KarimiDepartment of Medicine, McMaster University, Hamilton, ON, Canada.
Vanessa AshthorpeCentral Animal Facility, McMaster University, Hamilton, ON, Canada.
Minesh KapadiaDepartment of Psychiatry & Behavioral Neurosciences, McMaster University, Hamilton, ON, Canada.
Hui ZhaoDepartment of Psychiatry & Behavioral Neurosciences, McMaster University, Hamilton, ON, Canada.
Paulina DavisDepartment of Molecular & Biomedical Pharmacology, Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
Boris SakicDepartment of Psychiatry & Behavioral Neurosciences, McMaster University, Hamilton, ON, Canada.
McMaster University · CAUniversity of Kentucky · US

Funding

Kentucky Center for Clinical and Translational ScienceUL1TR000117 · NCATS · UNIVERSITY OF KENTUCKY · PI KERN, PHILIP A · 2012 to 2015
$13.3M
Kentucky Center for Clinical and Translational ScienceTL1TR000115 · NCATS · UNIVERSITY OF KENTUCKY · PI KERN, PHILIP A · 2012 to 2015
$518k
NCATS NIH HHS TL1 TR000115NCATS NIH HHS UL1 TR000117
6 · The paper itself

Abstract

backgroundImmune system activation is frequently reported in patients with Alzheimer's disease (AD). However, it remains unknown whether this is a cause, a consequence, or an epiphenomenon of brain degeneration.

objectiveThe present study examines whether immunological abnormalities occur in a well-established murine AD model and if so, how they relate temporally to behavioral deficits and neuropathology.

methodsA broad battery of tests was employed to assess behavioral performance and autoimmune/inflammatory markers in 3xTg-AD (AD) mice and wild type controls from 1.5 to 12 months of age.

resultsAged AD mice displayed severe manifestations of systemic autoimmune/inflammatory dise6ase, as evidenced by splenomegaly, hepatomegaly, elevated serum levels of anti-nuclear/anti-dsDNA antibodies, low hematocrit, and increased number of double-negative T splenocytes. However, anxiety-related behavior and altered spleen function were evident as early as 2 months of age, thus preceding typical AD-like brain pathology. Moreover, AD mice showed altered olfaction and impaired "cognitive" flexibility in the first 6 months of life, suggesting mild cognitive impairment-like manifestations before general learning/memory impairments emerged at an older age. Interestingly, all of these features were present in 3xTg-AD mice prior to significant amyloid-β or tau pathology.

conclusionThe results indicate that behavioral deficits in AD mice develop in parallel with systemic autoimmune/inflammatory disease. These changes antedate AD-like neuropathology, thus supporting a causal link between autoimmunity and aberrant behavior. Consequently, 3xTg-AD mice may be a useful model in elucidating the role of immune system in the etiology of AD.

Indexed as

Alzheimer DiseaseAnimalsAntibodies, AntinuclearAutoantibodiesBiomarkersBrainDisease Models, AnimalHematocritKidneyLiverLymphocyte CountMaleMaze LearningMiceMice, Inbred C57BLMice, TransgenicAntibodies, AntinuclearAutoantibodiesBiomarkers3xTg-AD modelAlzheimer's diseaseamyloidosisanxietyautoimmunityhepatomegalyinflammationmild cognitive impairmentolfactionsplenomegaly

Identifiers

PMID24150111
PMCPMC4376359
OpenAlexW1485278160

What Socratic 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 Socratic graph.