Lananna BV, McKee CA, King MW, Del-Aguila JL, Dimitry JM, Farias FH, Nadarajah CJ, Xiong DD, Guo C, Cammack AJ, Elias JA, Zhang J, Cruchaga C, Musiek ES. Chi3l1/YKL-40 is controlled by the astrocyte circadian clock and regulates neuroinflammation and Alzheimer's disease pathogenesis. Sci Transl Med. 2020 Dec 16;12(574) PubMed.

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  1. YKL-40 has been measured in CSF in the context of neurodegenerative disease for several years and is typically considered an indicator of activated astrocytes. Here, through a comprehensive series of experiments, the Musiek lab and collaborators provide far more information on YKL-40 than we’ve had previously.

    Among the interesting findings is the fact that individuals who carry a genetic polymorphism resulting in lower CSF YKL-40 appear to have attenuated cognitive decline. Furthermore, the animal and cell experiments suggest that YKL-40 may impact plaque burden in the brain via modulation of microglial phagocytosis of amyloid. It would be interesting to see if the impact of YKL-40 on amyloid is also supported by human studies. For example, do carriers of the genetic variant of the CHI3L1 gene that causes lower CSF YKL-40 concentrations also show attenuated amyloid accumulation?

    Additionally, this study provides data showing that the astrocyte circadian clock regulates Chi3l1 transcription. It is too early to tell how this links abnormalities in human sleep and AD pathology, but the study does provide intriguing new information pointing toward a role for glia in the sleep/AD connection.  

    View all comments by Barbara Bendlin

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