Lee E, Jung YJ, Park YR, S Li, Choi YJ, Lee SY, Kim CH, Mun JY, Chung WS. A distinct astrocyte subtype in the aging mouse brain characterized by impaired protein homeostasis. Nat Aging (2022). Nature Aging

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  1. These are interesting results. However, it is worth noting that such astrocytes have been described before, and some of the "vacuoles" are in fact polyglucosan bodies (Jucker et al., 1992; Jucker et al., 1994; comment on Baglietto-Vargas et al., 2021). Such astrocytic inclusions occur mainly in B6 mice and to a lesser degree in other mouse strains, and they have a strong genetic component. They tend to be sticky, and thus they can bind some antibodies non-specifically.

    Polyglucosan bodies occur in glial cells or neurons of humans; for example, corpora amylacea are astrocytic inclusions of still uncertain functional significance, and intraneuronal polyglucosan bodies are linked to rare neurodegenerative disorders such as Lafora disease and adult polyglucosan body disease (Cavanagh, 1999; Nitschke et al., 2018; Cenacchi et al., 2019). 

    Polyglucosan bodies of various types also occur naturally in a variety of animal species. The current publication now hopefully stimulates the field again to work on the nature and functional consequences of these abnormalities in the nervous system.

    References:

    Jucker M, Walker LC, Martin LJ, Kitt CA, Kleinman HK, Ingram DK, Price DL. Age-associated inclusions in normal and transgenic mouse brain. Science. 1992 Mar 13;255(5050):1443-5. PubMed.

    Jucker M, Walker LC, Schwarb P, Hengemihle J, Kuo H, Snow AD, Bamert F, Ingram DK. Age-related deposition of glia-associated fibrillar material in brains of C57BL/6 mice. Neuroscience. 1994 Jun;60(4):875-89. PubMed.

    Baglietto-Vargas D, Forner S, Cai L, Martini AC, Trujillo-Estrada L, Swarup V, Nguyen MM, Do Huynh K, Javonillo DI, Tran KM, Phan J, Jiang S, Kramár EA, Nuñez-Diaz C, Balderrama-Gutierrez G, Garcia F, Childs J, Rodriguez-Ortiz CJ, Garcia-Leon JA, Kitazawa M, Shahnawaz M, Matheos DP, Ma X, Da Cunha C, Walls KC, Ager RR, Soto C, Gutierrez A, Moreno-Gonzalez I, Mortazavi A, Tenner AJ, MacGregor GR, Wood M, Green KN, LaFerla FM. Generation of a humanized Aβ expressing mouse demonstrating aspects of Alzheimer's disease-like pathology. Nat Commun. 2021 Apr 23;12(1):2421. PubMed.

    Cavanagh JB. Corpora-amylacea and the family of polyglucosan diseases. Brain Res Brain Res Rev. 1999 Apr;29(2-3):265-95. PubMed.

    Nitschke F, Ahonen SJ, Nitschke S, Mitra S, Minassian BA. Lafora disease - from pathogenesis to treatment strategies. Nat Rev Neurol. 2018 Oct;14(10):606-617. PubMed.

    Cenacchi G, Papa V, Costa R, Pegoraro V, Marozzo R, Fanin M, Angelini C. Update on polyglucosan storage diseases. Virchows Arch. 2019 Dec;475(6):671-686. Epub 2019 Jul 30 PubMed.

    View all comments by Lary Walker

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