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@ARTICLE{Mengel:279379,
      author       = {Mengel, David and Soter, Ester and Ott, Julia-Maren and
                      Wacker, Madeleine and Leyva, Alejandra and Peters, Oliver
                      and Hellmann-Regen, Julian David Nicolai and Schneider,
                      Luisa-Sophie and Wang, Victoria Lingxiao and Priller, Josef
                      and Spruth, Eike Jakob and Altenstein, Slawek and Schneider,
                      Anja and Fließbach, Klaus and Wiltfang, Jens and Hansen,
                      Niels and Rostamzadeh, Ayda and Düzel, Emrah and Glanz,
                      Wenzel and Incesoy, Enise and Bürger, Katharina and
                      Janowitz, Daniel and Ewers, Michael and Perneczky, Robert
                      and Rauchmann, Boris Stephan and Teipel, Stefan and
                      Kilimann, Ingo and Laske, Christoph and Sodenkamp, Sebastian
                      and Spottke, Annika and Brustkern, Johanna and Brosseron,
                      Frederic and Wagner, Michael and Stark, Melina and
                      Kleineidam, Luca and Kai, Shao and Lüsebrink-Rindsland,
                      Jann Falk Silvester and Yakupov, Renat and Schmid, Matthias
                      and Hetzer, Stefan and Dechent, Peter and Scheffler, Klaus
                      and Berron, David and Jessen, Frank and Synofzik, Matthis},
      collaboration = {group, DELCODE study},
      title        = {{B}lood biomarkers confirm subjective cognitive decline
                      ({SCD}) as a distinct molecular and clinical stage within
                      the {NIA}-{AA} framework of {A}lzheimer´s disease.},
      journal      = {Molecular psychiatry},
      volume       = {30},
      number       = {7},
      issn         = {1359-4184},
      address      = {[London]},
      publisher    = {Springer Nature},
      reportid     = {DZNE-2025-00756},
      pages        = {3150 - 3159},
      year         = {2025},
      abstract     = {Subjective cognitive decline (SCD) is proposed as an
                      indicator of transitional disease stage 2 in the Alzheimer's
                      disease (AD) continuum. However, molecular and particularly
                      longitudinal fluid biomarker data for this stage are still
                      limited. This study aimed to determine whether blood-based
                      biomarkers in amyloid-positive individuals with SCD (A +
                      SCD) support the notion of stage 2 as a distinct stage
                      between stages 1 and 3 of AD and to identify those at high
                      risk for clinical progression. In a prospective multicenter
                      study (DELCODE) involving 457 participants across the AD
                      continuum, we analyzed plasma phospho-tau 181 (p181) and
                      neurofilament light chain (NfL) and assessed their
                      association with longitudinal cognition, hippocampal
                      atrophy, and AD clinical stage transition. The results
                      showed that baseline plasma p181 levels were elevated and
                      increased more rapidly in A + SCD individuals compared to
                      amyloid-positive cognitively unimpaired (A + CU) individuals
                      (stage 1). NfL levels rose across A + CU, A + SCD, and
                      amyloid-positive mild cognitive impairment (A + MCI, stage
                      3). In A + SCD, but not in A + CU, higher p181 levels
                      predicted cognitive decline (PACC5) and transition to MCI.
                      In conclusion, plasma p181 provides molecular biomarker
                      evidence supporting A + SCD as a pre-dementia AD stage
                      (stage 2) distinct from A + CU (stage 1) and helps identify
                      individuals at risk for cognitive decline early in the AD
                      continuum.},
      keywords     = {Humans / Cognitive Dysfunction: blood / Cognitive
                      Dysfunction: diagnosis / Cognitive Dysfunction: metabolism /
                      Male / Alzheimer Disease: blood / Alzheimer Disease:
                      metabolism / Female / Biomarkers: blood / Aged /
                      Neurofilament Proteins: blood / Disease Progression / tau
                      Proteins: blood / Prospective Studies / Aged, 80 and over /
                      Amyloid beta-Peptides: blood / United States / Hippocampus:
                      pathology / Longitudinal Studies / Atrophy /
                      Neuropsychological Tests / Cognition: physiology / Middle
                      Aged / Biomarkers (NLM Chemicals) / Neurofilament Proteins
                      (NLM Chemicals) / neurofilament protein L (NLM Chemicals) /
                      tau Proteins (NLM Chemicals) / Amyloid beta-Peptides (NLM
                      Chemicals)},
      cin          = {AG Gasser / AG Peters / AG Endres / AG Dirnagl / AG Priller
                      / AG Schneider / AG Wiltfang / Patient Studies (Bonn) / AG
                      Düzel / Clinical Research (Munich) / AG Dichgans / AG
                      Teipel / ICRU / AG Spottke / AG Wagner / AG Heneka / AG
                      Schmid Bonn / AG Berron / AG Jessen},
      ddc          = {610},
      cid          = {I:(DE-2719)1210000 / I:(DE-2719)5000000 /
                      I:(DE-2719)1811005 / I:(DE-2719)1810002 / I:(DE-2719)5000007
                      / I:(DE-2719)1011305 / I:(DE-2719)1410006 /
                      I:(DE-2719)1011101 / I:(DE-2719)5000006 / I:(DE-2719)1111015
                      / I:(DE-2719)5000022 / I:(DE-2719)1510100 /
                      I:(DE-2719)1240005 / I:(DE-2719)1011103 / I:(DE-2719)1011201
                      / I:(DE-2719)1011303 / I:(DE-2719)1013028 /
                      I:(DE-2719)5000070 / I:(DE-2719)1011102},
      pnm          = {353 - Clinical and Health Care Research (POF4-353) / 899 -
                      ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-899},
      experiment   = {EXP:(DE-2719)DELCODE-20140101},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40247130},
      pmc          = {pmc:PMC12185333},
      doi          = {10.1038/s41380-025-03021-0},
      url          = {https://pub.dzne.de/record/279379},
}