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Cited by 9Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Glial cell transcriptome analyses in 3xTg-AD mice: Effects of aging, disease progression, and anti-Aβ immunotherapy

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Lambracht-Washington, Doris, Fu, Min, Manouchehri, Navid, Hynan, Linda S., Stuve, Olaf, Rosenberg, Roger N.·2023·Aging Brain
DOI 10.1016/j.nbas.2023.100066PMC PMC9997156
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Abstract

Background: To investigate how changes in expression of glial genes relate to a progression of Alzheimer's disease (AD) pathology, and how anti-Aβ immunotherapy impact these changes, we conducted a transcriptomic analysis for brains from cohorts of 2-, 10-, and 20 month old 3xTg-AD mice, and a cross-sectional study in groups of 20 month-old mice treated with active DNA Aβ42 immunization, passive immunotherapy, untreated, and wild-type (wt) controls. Methods: Twenty-four Formalin-Fixed Paraffin-Embedded (FFPE) mouse brain sections were used for the gene expression analyses (nanostring). Adjacent sections from these and additional mouse brains were stained for microglia using antibodies detecting IbaI and Gal3. For a semi-quantitative analysis of increased tau and amyloid pathology with aging and disease progression, a comparison of ELISA results from brains of 12 and 20 months old 3xTg-AD mice were shown. Results: Based on the different comparisons of transcript numbers found the 3xTg-AD age groups with the senescent 20 months old wt control mouse brains, and the 20 months old 3xTg-AD mouse brains with the 20 months old wt control mouse brains, genes were assigned as upregulated due to aging, or due to disease progression, or due to both. The immunohistochemistry of microglia markers revealed that Gal3 might be an important marker for phagocytosing microglia around amyloid plaques. The comparison of the two anti-Aβ immunotherapy approaches showed a differential downregulation of inflammatory glial genes. Conclusion: These results are relevant for future clinical trials using active anti-amyloid immunotherapy.

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Cited by

Sorted by citations

Authors
Lambracht-Washington, D., Fu, M., Manouchehri, N., Hynan, L. S., Stuve, O., & Rosenberg, R. N.
Affiliations
The University of Texas Southwestern Medical Center (US)
ORCID
Venue
Aging Brain
Publisher
Elsevier BV
Published
2023
Volume
3
Pages
100066
ISSN
2589-9589 (ISSN-L)
DOI
10.1016/j.nbas.2023.100066
PMC
PMC9997156
OpenAlex
W4317938504
Cited by
9
References
5
Citations by year
2026: 1 · 2024: 8
FWCI
2.99
Type
journal article
Language
en
Open access
Licence
Locations
  • Aging Brain (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institutes of Health
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, glial cells, 3xTg-AD mice, aging, disease progression, anti-amyloid immunotherapy, passive immunotherapy, microglia, galectin-3, Iba1, amyloid plaques, tau pathology, neuroinflammation, gene expression

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