Home > Publications Database > Blood biomarkers confirm subjective cognitive decline (SCD) as a distinct molecular and clinical stage within the NIA-AA framework of Alzheimer´s disease. > print

001     279379
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024 7 _ |a 10.1038/s41380-025-03021-0
|2 doi
024 7 _ |a pmid:40247130
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024 7 _ |a pmc:PMC12185333
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024 7 _ |a 1359-4184
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024 7 _ |a 1476-5578
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037 _ _ |a DZNE-2025-00756
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Mengel, David
|0 P:(DE-2719)9000375
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245 _ _ |a Blood biomarkers confirm subjective cognitive decline (SCD) as a distinct molecular and clinical stage within the NIA-AA framework of Alzheimer´s disease.
260 _ _ |a [London]
|c 2025
|b Springer Nature
336 7 _ |a article
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336 7 _ |a ARTICLE
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520 _ _ |a 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.
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650 _ 7 |a Biomarkers
|2 NLM Chemicals
650 _ 7 |a Neurofilament Proteins
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650 _ 7 |a neurofilament protein L
|2 NLM Chemicals
650 _ 7 |a tau Proteins
|2 NLM Chemicals
650 _ 7 |a Amyloid beta-Peptides
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Cognitive Dysfunction: blood
|2 MeSH
650 _ 2 |a Cognitive Dysfunction: diagnosis
|2 MeSH
650 _ 2 |a Cognitive Dysfunction: metabolism
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Alzheimer Disease: blood
|2 MeSH
650 _ 2 |a Alzheimer Disease: metabolism
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Biomarkers: blood
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Neurofilament Proteins: blood
|2 MeSH
650 _ 2 |a Disease Progression
|2 MeSH
650 _ 2 |a tau Proteins: blood
|2 MeSH
650 _ 2 |a Prospective Studies
|2 MeSH
650 _ 2 |a Aged, 80 and over
|2 MeSH
650 _ 2 |a Amyloid beta-Peptides: blood
|2 MeSH
650 _ 2 |a United States
|2 MeSH
650 _ 2 |a Hippocampus: pathology
|2 MeSH
650 _ 2 |a Longitudinal Studies
|2 MeSH
650 _ 2 |a Atrophy
|2 MeSH
650 _ 2 |a Neuropsychological Tests
|2 MeSH
650 _ 2 |a Cognition: physiology
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
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773 _ _ |a 10.1038/s41380-025-03021-0
|g Vol. 30, no. 7, p. 3150 - 3159
|0 PERI:(DE-600)1502531-7
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|p 3150 - 3159
|t Molecular psychiatry
|v 30
|y 2025
|x 1359-4184
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