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

Abstract

Background: Several preclinical studies have reported elevated levels of tau following the induction of chronic cerebral hypoperfusion (CCH) in Alzheimer's disease mouse models. The objective of this study was to first induce CCH in a mouse model of tauopathy over an extended period of up to 6 months and to subsequently investigate the effects of CCH on tau accumulation and alterations in the transcriptome.

Methods: Three-month-old P301S tauopathy mice were randomly allocated to either a Sham or CCH group. The common carotid arteries (CCAs) of the CCH group were bilaterally implanted using 0.75-mm inner diameter ameroid constrictors. Prior to surgery, Doppler ultrasound imaging was acquired, with follow-up imaging at 1, 3, and 6 months postoperatively. Brain tissue samples were obtained, and hemispheres were dissected and divided for separate analysis.

Result: No significant differences in phosphorylated and total tau protein levels were found in either Sham or CCH left cortical hemispheres or hippocampal lysates. Immunohistochemical staining of phosphorylated tau in the right hemisphere revealed similar findings. Compared with the Sham group, transcriptomic deconvolution revealed a significant reduction of memory B cells in the CCH group (p = 0.029).

Conclusion: To clarify the effects of chronic hypoperfusion on tau pathology, more than one surgical method of hypoperfusion should be used in future studies.

Keywords: ameroid constrictor; chronic cerebral hypoperfusion; common carotid artery; tau; tauopathy.