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A Pilot Study on the Repetitive Transcranial Magnetic Stimulation of Aβ and Tau Levels in Rhesus Monkey Cerebrospinal Fluid
Published on: September 3, 2021
Trait-linked brainstem circuit resilience balances tau pathology-induced cellular vulnerability in Alzheimer's
Jie-Qun Zheng1, Hong-Wei Fan1, Chengye Yao2
1Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Abstract:
Although tau pathology correlates with cognitive decline in Alzheimer's disease (AD), some individuals exhibit resilience by maintaining cognitive function. The mechanisms enabling this protection, particularly before widespread cortical degeneration occurs, remain elusive. Here, we identify a dynamic interplay between cellular vulnerability and circuit-level resilience that shapes cognitive outcomes in AD. Tau accumulation in the Edinger-Westphal nucleus (EW) impairs attention by inducing hypoexcitability in CART+ neurons via Kcnma1 upregulation, a vulnerability predictive of future decline in both 3×Tg-AD mice and AD patients. Conversely, a subset of AD mice with heightened exploratory behavior activates a compensatory medial parabrachial (mPB)-EW circuit, mediated by substance P-Tacr1 signaling, which sustains CART+ neuron function and delays cognitive deterioration. These findings reveal resilience as an active state enabled by trait-linked circuit plasticity that balances cellular vulnerability, defining multilevel targets for early intervention.
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