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@ARTICLE{Frank:266800,
      author       = {Frank, Anika and Bendig, Jonas and Schnalke, Nils and
                      Klingelhoefer, Lisa and Reichmann, Heinz and Akgün, Katja
                      and Ziemssen, Tjalf and Falkenburger, Björn H},
      title        = {{S}erum neurofilament indicates accelerated
                      neurodegeneration and predicts mortality in late-stage
                      {P}arkinson's disease.},
      journal      = {npj Parkinson's Disease},
      volume       = {10},
      number       = {1},
      issn         = {2373-8057},
      address      = {London [u.a.]},
      publisher    = {Nature Publ. Group},
      reportid     = {DZNE-2024-00052},
      pages        = {14},
      year         = {2024},
      abstract     = {Different stages of Parkinson's disease (PD) are defined by
                      clinical criteria, while late-stage PD is marked by the
                      onset of morbidity milestones and rapid clinical
                      deterioration. Based on neuropathological evidence,
                      degeneration in the dopaminergic system occurs primarily in
                      the early stage of PD, raising the question of what drives
                      disease progression in late-stage PD. This study aimed to
                      investigate whether late-stage PD is associated with
                      increased neurodegeneration dynamics rather than functional
                      decompensation using the blood-based biomarker serum
                      neurofilament light chain (sNfL) as a proxy for the rate of
                      neurodegeneration. The study included 118 patients with PD
                      in the transition and late-stage (minimum disease duration 5
                      years, mean (SD) disease duration 15 (±7) years). The
                      presence of clinical milestones (hallucinations, dementia,
                      recurrent falls, and admission to a nursing home) and
                      mortality were determined based on chart review. We found
                      that sNfL was higher in patients who presented with at least
                      one clinical milestone and increased with a higher number of
                      milestones (Spearman's ρ = 0.66, p < 0.001). Above a cutoff
                      value of 26.9 pg/ml, death was 13.6 times more likely during
                      the follow-up period $(95\%$ CI: 3.53-52.3, p < 0.001),
                      corresponding to a sensitivity of $85.0\%$ and a specificity
                      of $85.7\%$ (AUC 0.91, $95\%$ CI: 0.85-0.97). Similar values
                      were obtained when using an age-adjusted cutoff percentile
                      of $90\%$ for sNfL. Our findings suggest that the rate of
                      ongoing neurodegeneration is higher in advanced PD (as
                      defined by the presence of morbidity milestones) than in
                      earlier disease stages. A better understanding of the
                      biological basis of stage-dependent neurodegeneration may
                      facilitate the development of neuroprotective means.},
      cin          = {AG Falkenburger / AG Kempermann},
      ddc          = {610},
      cid          = {I:(DE-2719)1710012 / I:(DE-2719)1710001},
      pnm          = {353 - Clinical and Health Care Research (POF4-353) / 352 -
                      Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC10776839},
      pubmed       = {pmid:38195715},
      doi          = {10.1038/s41531-023-00605-x},
      url          = {https://pub.dzne.de/record/266800},
}