Accelerated aging exacerbates a pre-existing pathology in a tau transgenic mouse model

Area of Science:

• Neuroscience
• Gerontology
• Genetics

Background:

• Age is a critical factor in tauopathies like Alzheimer's disease.
• Understanding the interaction between aging and tau pathology is crucial.
• Existing mouse models do not fully capture the complexity of age-related tauopathy.

Purpose of the Study:

• To investigate how an accelerated aging phenotype affects pathological tau accumulation.
• To establish and characterize a novel mouse model combining tauopathy and accelerated aging.
• To explore the impact of this combined phenotype on behavior and cognitive function.

Main Methods:

• Development of the SApT mouse strain by back-crossing pR5 tauopathy mice onto a SAMP8 accelerated aging background.
• Immunohistochemical analysis of tau phosphorylation in brain regions (amygdala, hippocampus).
• Behavioral testing including anxiety and learning/memory assessments.

Main Results:

• SApT mice exhibited increased pathological tau phosphorylation in the amygdala and hippocampus compared to pR5 mice.
• Tau phosphorylation showed an age-dependent increase in SApT mice.
• Older SApT mice displayed altered anxiety-like behavior, while learning and memory were impaired, resembling the SAMP8 background.

Conclusions:

• Accelerated aging exacerbates pathological tau phosphorylation and leads to behavioral changes.
• The SApT mouse model is a valuable tool for studying the interplay of aging and tauopathy.
• This model can help elucidate the role of geriatric phenotypes in neurodegenerative diseases.