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A 4R tauopathy develops without amyloid deposits in aged cat brains
Luc Poncelet1, Kunie Ando2, Cristina Vergara2
1Laboratory of Anatomy, Biomechanics and Organogenesis, ULB neuroscience institute, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
Neurobiology of Aging
|July 16, 2019
Summary
Aged cats spontaneously develop tau pathology, a hallmark of human neurodegenerative diseases like Alzheimer's. This naturally occurring feline tauopathy, independent of amyloid, offers insights into disease mechanisms and potential therapeutic targets.
Area of Science:
- Neuroscience
- Pathology
- Veterinary Medicine
Background:
- Human tauopathies are characterized by abnormal tau protein phosphorylation and aggregation, leading to neurofibrillary tangles.
- Aging is a significant risk factor for neurodegenerative diseases, including tauopathies.
Purpose of the Study:
- To investigate the spontaneous development of tau pathology in aged cat brains as a model for human tauopathies.
- To determine if tau pathology in cats occurs independently of amyloid deposits.
Main Methods:
- Examined brains from aged cats (18-21 years) for phosphorylated and aggregated tau.
- Utilized immunohistochemistry to detect tau pathology, amyloid, and glycogen synthase kinase-3 (GSK3).
- Assessed for cortical atrophy and neuronal loss in affected brains.
Main Results:
- Four out of six aged cats exhibited somatodendritic accumulation of phosphorylated and aggregated tau in neurons and oligodendrocytes.
- Tau pathology was observed in two cats without amyloid immunoreactivity, indicating amyloid-independence.
- Tau inclusions comprised mainly 4R tau isoforms and straight filaments, colocalizing with active GSK3.
- Affected cat brains showed significant cortical atrophy and neuronal loss.
Conclusions:
- Aged cat brains can spontaneously develop tau pathology, mirroring key aspects of human tauopathies.
- This feline model demonstrates tau pathology development independent of amyloid.
- The colocalization with active GSK3 suggests a shared mechanism in tau phosphorylation between cats and humans, offering a valuable comparative model.
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