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Cited by 94Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Autoimmune Manifestations in the 3xTg-AD Model of Alzheimer's Disease

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Marchese, Monica, Cowan, David, Head, Elizabeth, Ma, Donglai, Karimi, Khalil, Ashthorpe, Vanessa, Kapadia, Minesh, Zhao, Hui +2 more·2014·Journal of Alzheimer's Disease
DOI 10.3233/jad-131490PMC PMC4376359
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Abstract

BACKGROUND: Immune 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. OBJECTIVE: The 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. METHODS: A 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. RESULTS: Aged 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. CONCLUSION: The 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.

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Authors
Marchese, M., Cowan, D., Head, E., Ma, D., Karimi, K., Ashthorpe, V., Kapadia, M., Zhao, H., Davis, P., & Sakic, B.
Affiliations
  • McMaster University (CA)
  • University of Kentucky (US)
  • Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
  • Department of Psychiatry & Behavioral Neurosciences, McMaster University, Hamilton, ON, Canada
ORCID
Venue
Journal of Alzheimer's Disease
Publisher
SAGE Publications
Published
2014-01-07
Volume
39
Issue
1
Pages
191-210
ISSN
  • 1387-2877 (ISSN-L)
  • 1875-8908
DOI
10.3233/jad-131490
PMC
PMC4376359
OpenAlex
W1485278160
Cited by
94
References
12
Citations by year
2026: 4 · 2025: 8 · 2024: 13 · 2023: 4 · 2022: 4 · 2021: 11 · 2020: 6 · 2019: 7 · 2018: 10 · 2017: 7 · 2016: 8 · 2015: 8 · 2014: 4
FWCI
5.61
Type
journal article
Language
en
Open access
Locations
  • Journal of Alzheimer s Disease (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institutes of Health (TL1TR000115, UL1TR000117)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, 3xTg-AD mice
MeSH terms
Alzheimer Disease, Animals, Antibodies, Antinuclear, Autoantibodies, Brain, Disease Models, Animal, Hematocrit, Kidney, Liver, Male, Mice, Inbred C57BL, Mice, Transgenic, Organ Size, Spleen, Splenomegaly, T-Lymphocytes, Biomarkers, Lymphocyte Count, Maze Learning, Mice

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