Prolonged Chronic Cerebral Hypoperfusion Does not Exacerbate Tau Pathology in a Tauopathy Mouse Model

Na Kyung Lee ^1,2, Duk L Na ^2,3,4,5, Hee Jin Kim ^1,2,3,4,6

⁰Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, 06355 Seoul, Republic of Korea.

Journal of Integrative Neuroscience +

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February 28, 2025

View abstract on PubMed

Summary

Chronic cerebral hypoperfusion (CCH) did not alter tau levels in a mouse model of tauopathy. However, CCH significantly reduced memory B cells, suggesting complex effects beyond tau pathology.

Area Of Science

Neuroscience
Pathology
Immunology

Background

Preclinical studies suggest chronic cerebral hypoperfusion (CCH) elevates tau in Alzheimer's models.
Investigating CCH effects in tauopathy mouse models is crucial for understanding Alzheimer's disease progression.

Purpose Of The Study

To induce CCH in P301S tauopathy mice for up to 6 months.
To assess the impact of CCH on tau accumulation and transcriptome alterations.

Main Methods

P301S tauopathy mice underwent bilateral common carotid artery constriction (CCH) or sham surgery.
Doppler ultrasound monitored hypoperfusion; brain tissues were analyzed for tau and transcriptome changes.

Main Results

No significant differences in phosphorylated or total tau levels were observed between Sham and CCH groups.
Transcriptomic analysis revealed a significant reduction in memory B cells in the CCH group compared to Sham (p=0.029).

Conclusions

CCH did not increase tau pathology in this tauopathy mouse model.
Future research should employ diverse surgical methods to fully elucidate CCH's impact on tau pathology.

Keywords:

ameroid constrictor chronic cerebral hypoperfusion common carotid artery tau tauopathy