Cited by 15Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Detecting the effect of genetic diversity on brain composition in an Alzheimer’s disease mouse model

Open access
Gurdon, Brianna, Yates, Sharon C., Csucs, Gergely, Groeneboom, Nicolaas E., Hadad, Niran, Telpoukhovskaia, Maria, Ouellette, Andrew, Ouellette, Tionna +11 more·2024·Communications Biology

Published version of a preprint

Abstract

Alzheimer’s disease (AD) is broadly characterized by neurodegeneration, pathology accumulation, and cognitive decline. There is considerable variation in the progression of clinical symptoms and pathology in humans, highlighting the importance of genetic diversity in the study of AD. To address this, we analyze cell composition and amyloid-beta deposition of 6- and 14-month-old AD-BXD mouse brains. We utilize the analytical QUINT workflow- a suite of software designed to support atlas-based quantification, which we expand to deliver a highly effective method for registering and quantifying cell and pathology changes in diverse disease models. In applying the expanded QUINT workflow, we quantify near-global age-related increases in microglia, astrocytes, and amyloid-beta, and we identify strain-specific regional variation in neuron load. To understand how individual differences in cell composition affect the interpretation of bulk gene expression in AD, we combine hippocampal immunohistochemistry analyses with bulk RNA-sequencing data. This approach allows us to categorize genes whose expression changes in response to AD in a cell and/or pathology load-dependent manner. Ultimately, our study demonstrates the use of the QUINT workflow to standardize the quantification of immunohistochemistry data in diverse mice, - providing valuable insights into regional variation in cellular load and amyloid deposition in the AD-BXD model.

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  1. [90]Reprinted from Harnessing Genetic Complexity to Enhance Translatability of Alzheimer’s Disease Mouse Models: A Path toward Precision Medicine, Vol 101, Sarah M. Neuner, Sarah E. Heuer, Matthew J. Huentelman, Kristen M.S. O’Connell, Catherine C. Kaczorowski, Issue 3, 399-411, Copyright 2019, with permission from Elsevier. Reprinted from The Lancet, Vol. 101, Sarah M. Neuner, Sarah E. Heuer, Matthew J. Huentelman, Kristen M.S. O’Connell, Catherine C. Kaczorowski, Harnessing Genetic Complexity to Enhance Translatability of Alzheimer’s Disease Mouse Models: A Path toward Precision Medicine, 399-411, Copyright 2019, with permission from Elsevier. PMC6886697 30595332

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Authors
Gurdon, B., Yates, S. C., Csucs, G., Groeneboom, N. E., Hadad, N., Telpoukhovskaia, M., Ouellette, A., Ouellette, T., O’Connell, K. M. S., Singh, S., Murdy, T. J., Merchant, E., Bjerke, I., Kleven, H., Schlegel, U., Leergaard, T. B., Puchades, M. A., Bjaalie, J. G., & Kaczorowski, C. C.
Affiliations
  • Jackson Laboratory (US)
  • University of Oslo (NO)
  • Translational Genomics Research Institute (US)
  • Tufts University (US)
  • University of Michigan (US)
Corresponding author
  • Bjaalie, Jan G.
  • Kaczorowski, Catherine C.
Venue
Communications Biology
Published
2024-05-20
Volume
7
Issue
1
Pages
605-605
ISSN
2399-3642 (ISSN-L)
OpenAlex
W4398141685
Cited by
15
References
123
Citations by year
2026: 3 · 2025: 7 · 2024: 3 · 2023: 2
FWCI
3.70
Type
journal article
Language
en
Open access
Locations
  • Communications Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion, cc-by)
Funders
  • European Commission (945539)
  • Universitetet i Oslo
  • National Institute on Aging (R01AG057914, T32AG062409)
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, genetic diversity, amyloid-beta deposition, microglia, astrocytes, immunohistochemistry quantification, hippocampus, bulk RNA-seq, age-related neurodegeneration

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