Blood biomarkers confirm subjective cognitive decline (SCD) as a distinct molecular and clinical stage within the NIA-AA framework of Alzheimer´s disease
(2025) In Molecular Psychiatry 30(7). p.3150-3159- 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... (More)
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.
(Less)
- author
- author collaboration
- organization
- publishing date
- 2025-07
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Molecular Psychiatry
- volume
- 30
- issue
- 7
- pages
- 10 pages
- publisher
- Springer Nature
- external identifiers
-
- scopus:105003384720
- pmid:40247130
- ISSN
- 1359-4184
- DOI
- 10.1038/s41380-025-03021-0
- language
- English
- LU publication?
- yes
- id
- ccbe121a-01eb-4793-9c23-758430eb547b
- date added to LUP
- 2025-09-26 10:25:37
- date last changed
- 2025-10-14 12:10:33
@article{ccbe121a-01eb-4793-9c23-758430eb547b,
abstract = {{<p>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.</p>}},
author = {{Mengel, David and Soter, Ester and Ott, Julia Maren and Wacker, Madeleine and Leyva, Alejandra and Peters, Oliver and Hellmann-Regen, Julian and Schneider, Luisa Sophie and Wang, Xiao and Priller, Josef and Spruth, Eike and Altenstein, Slawek and Schneider, Anja and Fliessbach, Klaus and Wiltfang, Jens and Hansen, Niels and Rostamzadeh, Ayda and Düzel, Emra and Glanz, Wenzel and Incesoy, Enise I. and Buerger, Katharina and Janowitz, Daniel and Ewers, Michael and Perneczky, Robert and Rauchmann, Boris 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 Shao, Kai and Lüsebrink, Falk and Yakupov, Renat and Schmid, Matthias and Hetzer, Stefan and Dechent, Peter and Scheffler, Klaus and Berron, David and Jessen, Frank and Synofzik, Matthis}},
issn = {{1359-4184}},
language = {{eng}},
number = {{7}},
pages = {{3150--3159}},
publisher = {{Springer Nature}},
series = {{Molecular Psychiatry}},
title = {{Blood biomarkers confirm subjective cognitive decline (SCD) as a distinct molecular and clinical stage within the NIA-AA framework of Alzheimer´s disease}},
url = {{http://dx.doi.org/10.1038/s41380-025-03021-0}},
doi = {{10.1038/s41380-025-03021-0}},
volume = {{30}},
year = {{2025}},
}