Alzheimer's disease neuropathological characterization of the dog brain and relationship to biofluid biomarkers and cognitive function.
6 affiliations
- 1Department of Environmental & Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO USA.
- 2Brain Research Center, Colorado State University, Fort Collins, CO USA.
- 3Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA USA.
- 4College of Veterinary Medicine, University of Arizona, Tucson, AZ USA.
- 5University of California San Diego , Department of Pathology , San Diego, United States.
- 6Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO USA.
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.
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BibTeX
@article{alsulami2026alzheimers,
title = {{Alzheimer's disease neuropathological characterization of the dog brain and relationship to biofluid biomarkers and cognitive function.}},
author = {Abdullatif Alsulami and Marika Bogdani and Evan L MacLean and C Dirk Keene and Stephanie McGrath and Dog Aging Project Consortium and Caitlin S Latimer and Julie A Moreno},
journal = {NPJ dementia},
year = {2026},
month = oct,
doi = {10.1038/s44400-026-00141-4},
url = {https://europepmc.org/article/MED/42845905},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Alzheimer's disease neuropathological characterization of the dog brain and relationship to biofluid biomarkers and cognitive function.
AU - Abdullatif Alsulami
AU - Marika Bogdani
AU - Evan L MacLean
AU - C Dirk Keene
AU - Stephanie McGrath
AU - Dog Aging Project Consortium
AU - Caitlin S Latimer
AU - Julie A Moreno
PY - 2026
DA - 2026/10/06
JO - NPJ dementia
DO - 10.1038/s44400-026-00141-4
UR - https://europepmc.org/article/MED/42845905
AB - 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.
SN - 3005-1940
ER -