% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Groh:139268,
      author       = {Groh, Nicole and Bühler, Anika and Huang, Chaolie and Li,
                      Ka Wan and van Nierop, Pim and Smit, August B and Fändrich,
                      Marcus and Baumann, Frank and David, Della C},
      title        = {{A}ge-{D}ependent {P}rotein {A}ggregation {I}nitiates
                      {A}myloid-β {A}ggregation.},
      journal      = {Frontiers in aging neuroscience},
      volume       = {9},
      issn         = {1663-4365},
      address      = {Lausanne},
      publisher    = {Frontiers Research Foundation},
      reportid     = {DZNE-2020-05590},
      pages        = {138},
      year         = {2017},
      abstract     = {Aging is the most important risk factor for
                      neurodegenerative diseases associated with pathological
                      protein aggregation such as Alzheimer's disease. Although
                      aging is an important player, it remains unknown which
                      molecular changes are relevant for disease initiation.
                      Recently, it has become apparent that widespread protein
                      aggregation is a common feature of aging. Indeed, several
                      studies demonstrate that 100s of proteins become highly
                      insoluble with age, in the absence of obvious disease
                      processes. Yet it remains unclear how these misfolded
                      proteins aggregating with age affect neurodegenerative
                      diseases. Importantly, several of these aggregation-prone
                      proteins are found as minor components in disease-associated
                      hallmark aggregates such as amyloid-β plaques or
                      neurofibrillary tangles. This co-localization raises the
                      possibility that age-dependent protein aggregation directly
                      contributes to pathological aggregation. Here, we show for
                      the first time that highly insoluble proteins from aged
                      Caenorhabditis elegans or aged mouse brains, but not from
                      young individuals, can initiate amyloid-β aggregation in
                      vitro. We tested the seeding potential at four different
                      ages across the adult lifespan of C. elegans. Significantly,
                      protein aggregates formed during the early stages of aging
                      did not act as seeds for amyloid-β aggregation. Instead, we
                      found that changes in protein aggregation occurring during
                      middle-age initiated amyloid-β aggregation. Mass
                      spectrometry analysis revealed several late-aggregating
                      proteins that were previously identified as minor components
                      of amyloid-β plaques and neurofibrillary tangles such as
                      14-3-3, Ubiquitin-like modifier-activating enzyme 1 and
                      Lamin A/C, highlighting these as strong candidates for
                      cross-seeding. Overall, we demonstrate that widespread
                      protein misfolding and aggregation with age could be
                      critical for the initiation of pathogenesis, and thus should
                      be targeted by therapeutic strategies to alleviate
                      neurodegenerative diseases.},
      cin          = {AG David},
      ddc          = {610},
      cid          = {I:(DE-2719)1210004},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342)},
      pid          = {G:(DE-HGF)POF3-342},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:28567012},
      pmc          = {pmc:PMC5434662},
      doi          = {10.3389/fnagi.2017.00138},
      url          = {https://pub.dzne.de/record/139268},
}