TY  - JOUR
AU  - Mengel, David
AU  - Soter, Ester
AU  - Ott, Julia Maren
AU  - Wacker, Madeleine
AU  - Leyva, Alejandra
AU  - Peters, Oliver
AU  - Hellmann-Regen, Julian David Nicolai
AU  - Schneider, Luisa-Sophie
AU  - Wang, Xiao
AU  - Priller, Josef
AU  - Spruth, Eike Jakob
AU  - Altenstein, Slawek
AU  - Schneider, Anja
AU  - Fliessbach, Klaus
AU  - Wiltfang, Jens
AU  - Hansen, Niels
AU  - Rostamzadeh, Ayda
AU  - Düzel, Emra
AU  - Glanz, Wenzel
AU  - Incesoy, Enise I
AU  - Buerger, Katharina
AU  - Janowitz, Daniel
AU  - Ewers, Michael
AU  - Perneczky, Robert
AU  - Rauchmann, Boris Stephan
AU  - Teipel, Stefan
AU  - Kilimann, Ingo
AU  - Laske, Christoph
AU  - Sodenkamp, Sebastian
AU  - Spottke, Annika
AU  - Brustkern, Johanna
AU  - Brosseron, Frederic
AU  - Wagner, Michael
AU  - Stark, Melina
AU  - Kleineidam, Luca
AU  - Shao, Kai
AU  - Lüsebrink, Falk
AU  - Yakupov, Renat
AU  - Schmid, Matthias
AU  - Hetzer, Stefan
AU  - Dechent, Peter
AU  - Scheffler, Klaus
AU  - Berron, David
AU  - Jessen, Frank
AU  - Synofzik, Matthis
TI  - Blood biomarkers confirm subjective cognitive decline (SCD) as a distinct molecular and clinical stage within the NIA-AA framework of Alzheimer´s disease.
JO  - Molecular psychiatry
VL  - 30
IS  - 7
SN  - 1359-4184
CY  - [London]
PB  - Springer Nature
M1  - DZNE-2025-00756
SP  - 3150 - 3159
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Cognitive Dysfunction: blood
KW  - Cognitive Dysfunction: diagnosis
KW  - Cognitive Dysfunction: metabolism
KW  - Male
KW  - Alzheimer Disease: blood
KW  - Alzheimer Disease: metabolism
KW  - Female
KW  - Biomarkers: blood
KW  - Aged
KW  - Neurofilament Proteins: blood
KW  - Disease Progression
KW  - tau Proteins: blood
KW  - Prospective Studies
KW  - Aged, 80 and over
KW  - Amyloid beta-Peptides: blood
KW  - United States
KW  - Hippocampus: pathology
KW  - Longitudinal Studies
KW  - Atrophy
KW  - Neuropsychological Tests
KW  - Cognition: physiology
KW  - Middle Aged
KW  - Biomarkers (NLM Chemicals)
KW  - Neurofilament Proteins (NLM Chemicals)
KW  - neurofilament protein L (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
KW  - Amyloid beta-Peptides (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40247130
C2  - pmc:PMC12185333
DO  - DOI:10.1038/s41380-025-03021-0
UR  - https://pub.dzne.de/record/279379
ER  -