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@ARTICLE{Blmeke:909074,
      author       = {Blömeke, Lara and Pils, Marlene and Kraemer-Schulien,
                      Victoria and Dybala, Alexandra and Schaffrath, Anja and
                      Kulawik, Andreas and Rehn, Fabian and Cousin, Anneliese and
                      Nischwitz, Volker and Willbold, Johannes and Zack, Rebecca
                      and Tropea, Thomas F. and Bujnicki, Tuyen and Tamgüney,
                      Gültekin and Weintraub, Daniel and Irwin, David and
                      Grossman, Murray and Wolk, David A. and Trojanowski, John Q.
                      and Bannach, Oliver and Chen-Plotkin, Alice and Willbold,
                      Dieter},
      title        = {{Q}uantitative detection of α-{S}ynuclein and {T}au
                      oligomers and other aggregates by digital single particle
                      counting},
      journal      = {npj Parkinson's Disease},
      volume       = {8},
      number       = {1},
      issn         = {2373-8057},
      address      = {London [u.a.]},
      publisher    = {Nature Publ. Group},
      reportid     = {FZJ-2022-02992},
      pages        = {68},
      year         = {2022},
      abstract     = {The pathological hallmark of neurodegenerative diseases is
                      the formation of toxic oligomers by proteins such as
                      alpha-synuclein (aSyn) or microtubule-associated protein tau
                      (Tau). Consequently, such oligomers are promising biomarker
                      candidates for diagnostics as well as drug development.
                      However, measuring oligomers and other aggregates in human
                      biofluids is still challenging as extreme sensitivity and
                      specificity are required. We previously developed
                      surface-based fluorescence intensity distribution analysis
                      (sFIDA) featuring single-particle sensitivity and absolute
                      specificity for aggregates. In this work, we measured aSyn
                      and Tau aggregate concentrations of 237 cerebrospinal fluid
                      (CSF) samples from five cohorts: Parkinson's disease (PD),
                      dementia with Lewy bodies (DLB), Alzheimer's disease (AD),
                      progressive supranuclear palsy (PSP), and a
                      neurologically-normal control group. aSyn aggregate
                      concentration discriminates PD and DLB patients from normal
                      controls (sensitivity $73\%,$ specificity $65\%,$ area under
                      the receiver operating curve (AUC) 0.68). Tau aggregates
                      were significantly elevated in PSP patients compared to all
                      other groups (sensitivity $87\%,$ specificity $70\%,$ AUC
                      0.76). Further, we found a tight correlation between aSyn
                      and Tau aggregate titers among all patient cohorts (Pearson
                      coefficient of correlation r = 0.81). Our results
                      demonstrate that aSyn and Tau aggregate concentrations
                      measured by sFIDA differentiate neurodegenerative disease
                      diagnostic groups. Moreover, sFIDA-based Tau aggregate
                      measurements might be particularly useful in distinguishing
                      PSP from other parkinsonisms. Finally, our findings suggest
                      that sFIDA can improve pre-clinical and clinical studies by
                      identifying those individuals that will most likely respond
                      to compounds designed to eliminate specific oligomers or to
                      prevent their formation.},
      cin          = {IBI-7},
      ddc          = {610},
      cid          = {I:(DE-Juel1)IBI-7-20200312},
      pnm          = {5244 - Information Processing in Neuronal Networks
                      (POF4-524) / 520 - Natural, Artificial and Cognitive
                      Information Processing (POF4-500)},
      pid          = {G:(DE-HGF)POF4-5244 / G:(DE-HGF)POF4-520},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {35655068},
      UT           = {WOS:000805184000001},
      doi          = {10.1038/s41531-022-00330-x},
      url          = {https://juser.fz-juelich.de/record/909074},
}