Temporal progression of auditory brainstem dysfunction and behavioral phenotypes in mouse models of tauopathy

Topic: Brain proteins, microglia and lab models

The PS19 mouse model expressing the P301S tau mutation exhibits tau pathology associated with frontotemporal dementia. Together, these results demonstrate that auditory pathway dysfunction may represent an early marker of tau pathology preceding behavioral impairment. The divergent temporal patterns of ABR alterations across genotypes suggest that genetic context, particularly ApoE4, modulates the progression of tau-driven circuit dysfunction, highlighting ABR as a potential noninvasive biomarker for early tau-related neurodegenerative disease. Genetic background also significantly influenced disease progression, with the ApoE4 allele altering both the timing and nature of auditory and behavioral phenotypes. Together, these findings demonstrate that tau pathology disrupts auditory processing at early disease stages and suggest that ABR-based measures as sensitive, non-invasive approach for early detection and monitoring of tau-related neurodegeneration.

Key findings

• The PS19 mouse model expressing the P301S tau mutation exhibits tau pathology associated with frontotemporal dementia.
• Together, these results demonstrate that auditory pathway dysfunction may represent an early marker of tau pathology preceding behavioral impairment.
• The divergent temporal patterns of ABR alterations across genotypes suggest that genetic context, particularly ApoE4, modulates the progression of tau-driven circuit dysfunction, highlighting ABR as a potential noninvasive biomarker for early tau-related neurodegenerative disease.
• Genetic background also significantly influenced disease progression, with the ApoE4 allele altering both the timing and nature of auditory and behavioral phenotypes.
• Together, these findings demonstrate that tau pathology disrupts auditory processing at early disease stages and suggest that ABR-based measures as sensitive, non-invasive approach for early detection and monitoring of tau-related neurodegeneration.

Why it matters

In PS19 tauopathy mice, auditory brainstem dysfunction appeared before behavioral impairment, and the ApoE4 allele changed the timing and nature of these phenotypes. The authors propose auditory brainstem response measures as a potential noninvasive biomarker for early detection, not as a treatment.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1523/jneurosci.0511-26.2026
• PubMed: 42660657
• Original source →
• Free full text: Journal of Neuroscience →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

@article{nguyen2026-42660657,
  author  = {Nguyen, Ann M. and Lo, Helen and Fields, James and Cramer, Karina S. and Zeng, Fan‐Gang and Dong, Wei and Xu, Xiangmin},
  title   = {{Temporal progression of auditory brainstem dysfunction and behavioral phenotypes in mouse models of tauopathy}},
  journal = {Journal of Neuroscience},
  year    = {2026},
  doi     = {10.1523/jneurosci.0511-26.2026},
  pmid    = {42660657},
  url     = {https://doi.org/10.1523/jneurosci.0511-26.2026}
}

Related studies in Disease mechanisms

• Directionality bias underpins divergent spatiotemporal progression of Alzheimer‐related tauopathy in mouse models Alzheimer s & Dementia · 2025-05-01 · usefulness score 38/100
• Temporal transcriptomic changes in the THY-Tau22 mouse model of tauopathy display cell type- and sex-specific differences Acta Neuropathologica Communications · 2025-05-07 · usefulness score 42/100
• MAPT splicing modulators reduce 4R tau and rescue tauopathy phenotypes in human neurons and in a mouse model Science Translational Medicine · 2026-08-19 · usefulness score 40/100
• ApoE isoform- and microbiota-dependent progression of neurodegeneration in a mouse model of tauopathy Science (New York, N.Y.) · 2023-01-13 · usefulness score 45/100
• Differences in Synaptic Dysfunction Between rTg4510 and APP/PS1 Mouse Models of Alzheimer's Disease Journal of Alzheimer's disease : JAD · 2018 · usefulness score 39/100
• Twenty years of therapeutic development in tauopathy mouse models: a scoping review Alzheimer s & Dementia · 2025-08-01 · usefulness score 43/100

Similar studies

• Tauopathy-like abnormalities and neurologic deficits in mice immunized with neuronal tau protein 2006 · Disease mechanisms
• Accumulation of pathological tau species and memory loss in a conditional model of tauopathy 2007 · Lewy body dementia
• Comparative In Vitro and In Vivo Quantifications of Pathologic Tau Deposits and Their Association with Neurodegeneration in Tauopathy Mouse Models 2018 · Brain scans and imaging
• Tau and tauopathies across primate species: implications for modeling neurodegenerative disorders 2025 · Disease mechanisms
• Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls 2013 · Disease mechanisms
• Cell-mediated neuroprotection in a mouse model of human tauopathy 2010 · Disease mechanisms

More on Disease mechanisms

• A review that covers this ground Effects of triptolide herb on the progression of Alzheimer's disease preclinical models: a systematic review Neurodegenerative disease management · 2025-09-24 · usefulness score 42/100
• Newest in this subject Aβ42 oligomers disrupt calcium homeostasis via Piezo1 and induce neurotoxicity in differentiated SH-SY5Y cells Research Square · 2026-10-29 · Preprint — not yet peer-reviewed · usefulness score 16/100
• Newest in this subject Neuronal Hyperactivity Induces Tau Phosphorylation Selectively in Excitatory Pyramidal Neurons Which Contributes to GluA2 Regulation bioRxiv · 2026-10-28 · Preprint — not yet peer-reviewed · usefulness score 16/100

See all studies in Disease mechanisms →