• New information about amyloid filaments

    From ScienceDaily@1:317/3 to All on Mon Mar 28 22:30:40 2022
    New information about amyloid filaments in neurodegenerative diseases


    Date:
    March 28, 2022
    Source:
    Indiana University School of Medicine
    Summary:
    Researchers have helped identify that a common protein found
    in neurodegenerative diseases forms amyloid filaments in an
    age-dependent manner without a connection to disease.



    FULL STORY ========================================================================== Experts at Indiana University School of Medicine have helped identify
    that a common protein found in neurodegenerative diseases forms amyloid filaments in an age-dependent manner without a connection to disease.


    ==========================================================================
    Many age-dependent neurodegenerative diseases, like Alzheimer's and Parkinson's, are characterized by amyloid abundance, or plaque. In a
    new paper published in Nature, researchers from the MRC Laboratory of
    Molecular Biology in Cambridge, England, United Kingdom and colleagues
    around the world, including several IU School of Medicine experts,
    used electron cryo-microscopy structure determination to discover that lysosomal type II transmembrane protein, TMEM106B, also forms amyloid
    filaments in human brains but, uniquely, it forms in an age-dependent
    manner and might not be connected to a type of disease.

    "Until now, the presence of abundant intraneuronal amyloid filaments in
    human tissues has always been associated with disease," said Bernardino
    Ghetti, MD, a distinguished professor and professor of pathology and
    laboratory medicine at IU School of Medicine. "While TMEM106B has been associated with frontotemporal dementias and other diseases, the evidence
    for a causal relationship between TMEM106B aggregation and disease now
    remains unclear." Researchers studied 22 individuals with abundant
    amyloid deposits, including sporadic and inherited Alzheimer's, as well
    as the frontal cortex of three neurologically normal individuals. They
    also studied three TMEM106B folds, with no clear relationships between
    folds and diseases. The TMEM106B filaments discovered in the brains
    of older, but not younger, neurologically normal individuals suggests
    that these proteins form in an age-dependent manner and that there
    was no clear relationship between protein folds and neurodegenerative
    diseases. Previously, TMEM106B has been identified as a risk factor for frontotemporal lobar degeneration, but this research opens the dialogue
    as the protein may no longer be associated with the cause of a disease.

    "This insight encourages us to further assess the role of filament
    formation, like TMEM106B, in relation to human aging and other
    pathologies, as well as if they're found outside the nervous system,"
    Ghetti said.

    The study was supported by National Institutes of Health grants. Other
    study authors from IU School of Medicine include Holly Garringer, PhD,
    Grace Hallinan, PhD, Kathy Newell, MD and Ruben Vidal, PhD. Previously,
    this research group also explored the pathological differences in
    inherited versus sporadic Alzheimer's disease.


    ========================================================================== Story Source: Materials provided by
    Indiana_University_School_of_Medicine. Note: Content may be edited for
    style and length.


    ========================================================================== Journal Reference:
    1. Manuel Schweighauser, Diana Arseni, Mehtap Bacioglu, Melissa
    Huang, Sofia
    Lo"vestam, Yang Shi, Yang Yang, Wenjuan Zhang, Abhay Kotecha,
    Holly J.

    Garringer, Ruben Vidal, Grace I. Hallinan, Kathy L. Newell,
    Airi Tarutani, Shigeo Murayama, Masayuki Miyazaki, Yuko
    Saito, Mari Yoshida, Kazuko Hasegawa, Tammaryn Lashley,
    Tamas Revesz, Gabor G. Kovacs, John van Swieten, Masaki Takao,
    Masato Hasegawa, Bernardino Ghetti, Maria Grazia Spillantini,
    Benjamin Ryskeldi-Falcon, Alexey G. Murzin, Michel Goedert, Sjors
    H. W. Scheres. Age-dependent formation of TMEM106B amyloid filaments
    in human brains. Nature, 2022; DOI: 10.1038/s41586-022-04650-z ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/03/220328160645.htm

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