Decreased Orexin Receptor 1 mRNA Expression in the Locus Coeruleus in Both Tau Transgenic rTg4510 and Tau Knockout Mice and Accompanying Ascending Arousal System Tau Invasion in rTg4510
Ryan J Keenan, Sara Oberrauch, Romke Bron, Cameron J Nowell, Leesa M Challis, Daniel Hoyer, Laura H Jacobson
JOURNAL OF ALZHEIMERS DISEASE | IOS PRESS | Published : 2021
BACKGROUND: Sleep/wake disturbances (e.g., insomnia and sleep fragmentation) are common in neurodegenerative disorders, especially Alzheimer's disease (AD) and frontotemporal dementia (FTD). These symptoms are somewhat reminiscent of narcolepsy with cataplexy, caused by the loss of orexin-producing neurons. A bidirectional relationship between sleep disturbance and disease pathology suggests a detrimental cycle that accelerates disease progression and cognitive decline. The accumulation of brain tau fibrils is a core pathology of AD and FTD-tau and clinical evidence supports that tau may impair the orexin system in AD/FTD. This hypothesis was investigated using tau mutant mice. OBJECTIVE: To..View full abstract
Awarded by Alzheimer's Association Grant
The authors thank Andrew Lawrence, Sanjida Mir, Tina Carter, Leah Beauchamp, The Florey Advanced Microscopy and Immunohistochemistry Service, and the Imaging, FACS and Analysis Core (Monash Institute of Pharmaceutical Sciences) for expert technical assistance and advice. This work was funded by the Alzheimer's Association Grant 2016-NIRG-396905 to LHJ and DH. The Florey Institute of Neuroscience and Mental Health acknowledge the support of the Victorian Government and in particular the funding from the Operational Infrastructure Support Grant. Authors' disclosures available online (https://www.j-alz.com/manuscript-disclosures/20-1177r1).