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@ARTICLE{Chakrabarti:1030397,
      author       = {Chakrabarti, Kalyan S. and Bakhtiari, Davood and
                      Rezaei-Ghaleh, Nasrollah},
      title        = {{B}ifurcations in coupled amyloid-β
                      aggregation-inflammation systems},
      journal      = {npj Systems biology and applications},
      volume       = {10},
      number       = {1},
      issn         = {2056-7189},
      address      = {London},
      publisher    = {Nature Publ. Group},
      reportid     = {FZJ-2024-05276},
      pages        = {80},
      year         = {2024},
      abstract     = {A complex interplay between various processes underlies the
                      neuropathology of Alzheimer’s disease (AD) and its
                      progressive course. Several lines of evidence point to the
                      coupling between Aβ aggregation and neuroinflammation and
                      its role in maintaining brain homeostasis during the long
                      prodromal phase of AD. Little is however known about how
                      this protective mechanism fails and as a result, an
                      irreversible and progressive transition to clinical AD
                      occurs. Here, we introduce a minimal model of a coupled
                      system of Aβ aggregation and inflammation, numerically
                      simulate its dynamical behavior, and analyze its bifurcation
                      properties. The introduced model represents the following
                      events: generation of Aβ monomers, aggregation of Aβ
                      monomers into oligomers and fibrils, induction of
                      inflammation by Aβ aggregates, and clearance of various Aβ
                      species. Crucially, the rates of Aβ generation and
                      clearance are modulated by inflammation level following a
                      Hill-type response function. Despite its relative
                      simplicity, the model exhibits enormously rich dynamics
                      ranging from overdamped kinetics to sustained oscillations.
                      We then specify the region of inflammation- and
                      coupling-related parameters space where a transition to
                      oscillatory dynamics occurs and demonstrate how changes in
                      Aβ aggregation parameters could shift this oscillatory
                      region in parameter space. Our results reveal the propensity
                      of coupled Aβ aggregation-inflammation systems to
                      oscillatory dynamics and propose prolonged sustained
                      oscillations and their consequent immune system exhaustion
                      as a potential mechanism underlying the transition to a more
                      progressive phase of amyloid pathology in AD. The
                      implications of our results in regard to early diagnosis of
                      AD and anti-AD drug development are discussed.},
      cin          = {IBI-7},
      ddc          = {570},
      cid          = {I:(DE-Juel1)IBI-7-20200312},
      pnm          = {5241 - Molecular Information Processing in Cellular Systems
                      (POF4-524)},
      pid          = {G:(DE-HGF)POF4-5241},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {39080352},
      UT           = {WOS:001280917200001},
      doi          = {10.1038/s41540-024-00408-7},
      url          = {https://juser.fz-juelich.de/record/1030397},
}