ORCID: https://orcid.org/0000-0002-4133-7182; Soter, Ester; Ott, Julia Maren; Wacker, Madeleine; Leyva, Alejandra; Peters, Oliver; Hellmann-Regen, Julian ORCID: https://orcid.org/0000-0003-0411-9204; Schneider, Luisa-Sophie ORCID: https://orcid.org/0000-0001-5822-1744; Wang, Xiao; Priller, Josef; Spruth, Eike; Altenstein, Slawek; Schneider, Anja ORCID: https://orcid.org/0000-0001-9540-8700; Fliessbach, Klaus; Wiltfang, Jens ORCID: https://orcid.org/0000-0003-1492-5330; Hansen, Niels ORCID: https://orcid.org/0000-0001-5785-9594; Rostamzadeh, Ayda; Düzel, Emra; Glanz, Wenzel; Incesoy, Enise I.; Buerger, Katharina ORCID: https://orcid.org/0000-0002-5898-9953; Janowitz, Daniel ORCID: https://orcid.org/0009-0003-4090-547X; Ewers, Michael ORCID: https://orcid.org/0000-0001-5231-1714; Perneczky, Robert ORCID: https://orcid.org/0000-0003-1981-7435; Rauchmann, Boris-Stephan ORCID: https://orcid.org/0000-0003-4547-6240; Teipel, Stefan; Kilimann, Ingo; Laske, Christoph; Sodenkamp, Sebastian; Spottke, Annika; Brustkern, Johanna; Brosseron, Frederic ORCID: https://orcid.org/0000-0003-3137-7516; Wagner, Michael; Stark, Melina; Kleineidam, Luca ORCID: https://orcid.org/0009-0006-3309-6856; Shao, Kai; Lüsebrink, Falk; Yakupov, Renat ORCID: https://orcid.org/0000-0002-3868-284X; Schmid, Matthias; Hetzer, Stefan; Dechent, Peter; Scheffler, Klaus; Berron, David ORCID: https://orcid.org/0000-0003-1558-1883; Jessen, Frank und Synofzik, Matthis ORCID: https://orcid.org/0000-0002-2280-7273
(2025):
Blood biomarkers confirm subjective cognitive decline (SCD) as a distinct molecular and clinical stage within the NIA-AA framework of Alzheimer´s disease.
In: Molecular Psychiatry [Forthcoming]
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.
| Item Type: | Journal article |
|---|---|
| Faculties: | Medicine > Munich Cluster for Systems Neurology (SyNergy) Medicine > Institute for Stroke and Dementia Research (ISD) Medicine > Medical Center of the University of Munich > Clinic and Polyclinic for Psychiatry and Psychotherapy Medicine > Medical Center of the University of Munich > Clinic and Polyclinic for Radiology |
| Subjects: | 600 Technology > 610 Medicine and health |
| ISSN: | 1359-4184 |
| Annotation: | with the DELCODE study group; a complete list of the froup members can be found on the publisher's webpage. |
| Language: | English |
| Item ID: | 126043 |
| Date Deposited: | 21. May 2025 11:41 |
| Last Modified: | 21. May 2025 11:41 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198 |
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