Alzheimer’s disease neuropathological characterization of the dog brain and relationship to biofluid biomarkers and cognitive function

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting more than 55 million people worldwide and is characterized by cognitive decline, amyloid-beta (Aβ) plaques, and neurofibrillary tangles. Although transgenic rodent models have advanced understanding of AD, they do not fully replicate the spontaneous, age-related nature of human disease. Companion dogs naturally develop age-associated cognitive decline and AD-like neuropathology, making them a valuable translational model. This study characterized Aβ deposition, phosphorylated tau (pTau181) pathology, and neuritic plaque pathology in aged canine brains using neuropathologic assessment methods adapted from human AD frameworks (Thal, Braak, and CERAD), and examined associations with cognitive status and plasma biomarkers. Postmortem brain tissues from 24 client-owned senior dogs were evaluated and integrated with antemortem Canine Cognitive Dysfunction Rating (CCDR) scores and plasma biomarker measurements. Senior dogs exhibited Aβ deposition consistent with early Thal-like regional involvement, variable regionally restricted pTau181 pathology, and an absence of neuritic plaques. Quantitative analyses showed greater Aβ burden in cognitively impaired dogs, while age was the strongest predictor of regional Aβ accumulation. Plasma glial fibrillary acidic protein (GFAP) concentrations were positively correlated with Aβ plaque burden, whereas other biomarkers were not. These findings indicate that aged dogs develop early-stage AD-like pathology and support their utility as a naturally aging model for studying preclinical AD mechanisms and translational biomarkers.

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Publication Details

Journal
npj Dementia
Published
2026-10-06
DOI
https://doi.org/10.1038/s44400-026-00141-4
Primary Topic
Alzheimer's disease research and treatments
Type
article
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article

Alzheimer’s disease neuropathological characterization of the dog brain and relationship to biofluid biomarkers and cognitive function

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npj Dementia
Alzheimer's disease research and treatments
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Alzheimer’s disease neuropathological characterization of the dog brain and relationship to biofluid biomarkers and cognitive function

Daniel Promislow, Silvan R. Urfer, Marika Bogdani, Robyn L. McClelland, Brooke Benton, Mary Katherine Tolbert, Kathleen F. Kerr, Sandi Shrager, Amanda Erickson Coleman, Julie A. Moreno, Unity Jeffery, Stephanie McGrath, Kate E. Creevy, Stephen Mark Schwartz, Caitlin S. Latimer, Virginia R. Fajt, Noah Snyder‐Mackler, Elinor K. Karlsson, Benjamin S. Wilfond, Kyle D. Crowder, Elhanan Borenstein, Annette L. Fitzpatrick, Matt R. Kaeberlein, Matthew D. Dunbar, Abdullatif Alsulami, Erica C. Jonlin, Evan L. MacLean, Marta G. Castelhano, Joshua M. Akey, Jonathan M. Levine, C. Dirk Keene, Audrey Ruple, Jing Ma
article en

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting more than 55 million people worldwide and is characterized by cognitive decline, amyloid-beta (Aβ) plaques, and neurofibrillary tangles. Although transgenic rodent models have advanced understanding of AD, they do not fully replicate the spontaneous, age-related nature of human disease. Companion dogs naturally develop age-associated cognitive decline and AD-like neuropathology, making them a valuable translational model. This study characterized Aβ deposition, phosphorylated tau (pTau181) pathology, and neuritic plaque pathology in aged canine brains using neuropathologic assessment methods adapted from human AD frameworks (Thal, Braak, and CERAD), and examined associations with cognitive status and plasma biomarkers. Postmortem brain tissues from 24 client-owned senior dogs were evaluated and integrated with antemortem Canine Cognitive Dysfunction Rating (CCDR) scores and plasma biomarker measurements. Senior dogs exhibited Aβ deposition consistent with early Thal-like regional involvement, variable regionally restricted pTau181 pathology, and an absence of neuritic plaques. Quantitative analyses showed greater Aβ burden in cognitively impaired dogs, while age was the strongest predictor of regional Aβ accumulation. Plasma glial fibrillary acidic protein (GFAP) concentrations were positively correlated with Aβ plaque burden, whereas other biomarkers were not. These findings indicate that aged dogs develop early-stage AD-like pathology and support their utility as a naturally aging model for studying preclinical AD mechanisms and translational biomarkers.

npj DementiaVol. 2(1)
Broad Institute (US), Tufts University (US), Santa Fe Institute (US), University of Arizona (US), University of San Diego (US), Tel Aviv University (IL), University of Georgia (US), University of Massachusetts Chan Medical School (US), Princeton University (US), University of Washington (US), Cornell University (US), Fred Hutch Cancer Center (US), Jean Mayer Human Nutrition Research Center on Aging (US), New York State College of Veterinary Medicine (US), Seattle Children's Research Institute (US), Treuman Katz Center for Pediatric Bioethics and Palliative Care (US), Arizona State University (US), Virginia Tech (US), Texas A&M University (US), Colorado State University (US)
Openalex Percentile: Top 12%
Alzheimer's disease research and treatments
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