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A brainstem to circadian system circuit links Tau pathology to sundowning-related disturbances in an Alzheimer’s disease mouse model

Author

Listed:
  • Andrew E. Warfield

    (University of Wyoming)

  • Pooja Gupta

    (University of Wyoming)

  • Madison M. Ruhmann

    (University of Wyoming)

  • Quiana L. Jeffs

    (University of Wyoming)

  • Genevieve C. Guidone

    (University of Wyoming)

  • Hannah W. Rhymes

    (University of Wyoming)

  • McKenzi I. Thompson

    (Emory University)

  • William D. Todd

    (University of Wyoming)

Abstract

Alzheimer’s disease (AD) patients exhibit progressive disruption of entrained circadian rhythms and an aberrant circadian input pathway may underlie such dysfunction. Here we examine AD-related pathology and circadian dysfunction in the APPSwe-Tau (TAPP) model of AD. We show these mice exhibit phase delayed body temperature and locomotor activity with increases around the active-to-rest phase transition. Similar AD-related disruptions are associated with sundowning, characterized by late afternoon and early evening agitation and aggression, and we show TAPP mice exhibit increased aggression around this transition. We show such circadian dysfunction and aggression coincide with hyperphosphorylated Tau (pTau) development in lateral parabrachial (LPB) neurons, with these disturbances appearing earlier in females. Finally, we show LPB neurons, including those expressing dynorphin (LPBdyn), project to circadian structures and are affected by pTau, and LPBdyn ablations partially recapitulate the hyperthermia of TAPP mice. Altogether we link pTau in a brainstem circadian input pathway to AD-related disturbances relevant to sundowning.

Suggested Citation

  • Andrew E. Warfield & Pooja Gupta & Madison M. Ruhmann & Quiana L. Jeffs & Genevieve C. Guidone & Hannah W. Rhymes & McKenzi I. Thompson & William D. Todd, 2023. "A brainstem to circadian system circuit links Tau pathology to sundowning-related disturbances in an Alzheimer’s disease mouse model," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40546-w
    DOI: 10.1038/s41467-023-40546-w
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    1. William D. Todd & Anne Venner & Christelle Anaclet & Rebecca Y. Broadhurst & Roberto Luca & Sathyajit S. Bandaru & Lindsay Issokson & Lauren M. Hablitz & Olga Cravetchi & Elda Arrigoni & John N. Campb, 2020. "Suprachiasmatic VIP neurons are required for normal circadian rhythmicity and comprised of molecularly distinct subpopulations," Nature Communications, Nature, vol. 11(1), pages 1-20, December.
    2. Li Sun & Rui Liu & Fang Guo & Man-qing Wen & Xiao-lin Ma & Kai-yuan Li & Hao Sun & Ceng-lin Xu & Yuan-yuan Li & Meng-yin Wu & Zheng-gang Zhu & Xin-jian Li & Yan-qin Yu & Zhong Chen & Xiang-yao Li & Sh, 2020. "Parabrachial nucleus circuit governs neuropathic pain-like behavior," Nature Communications, Nature, vol. 11(1), pages 1-21, December.
    3. Jing Xiong & Seong Su Kang & Zhihao Wang & Xia Liu & Tan-Chun Kuo & Funda Korkmaz & Ashley Padilla & Sari Miyashita & Pokman Chan & Zhaohui Zhang & Pavel Katsel & Jocoll Burgess & Anisa Gumerova & Kse, 2022. "FSH blockade improves cognition in mice with Alzheimer’s disease," Nature, Nature, vol. 603(7901), pages 470-476, March.
    4. Steven M. Reppert & David R. Weaver, 2002. "Coordination of circadian timing in mammals," Nature, Nature, vol. 418(6901), pages 935-941, August.
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