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000279379 1001_ $$0P:(DE-2719)9000375$$aMengel, David$$b0$$eFirst author
000279379 245__ $$aBlood biomarkers confirm subjective cognitive decline (SCD) as a distinct molecular and clinical stage within the NIA-AA framework of Alzheimer´s disease.
000279379 260__ $$a[London]$$bSpringer Nature$$c2025
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000279379 520__ $$aSubjective cognitive decline (SCD) is proposed as an indicator of transitional disease stage 2 in the Alzheimer's disease (AD) continuum. However, molecular and particularly longitudinal fluid biomarker data for this stage are still limited. This study aimed to determine whether blood-based biomarkers in amyloid-positive individuals with SCD (A + SCD) support the notion of stage 2 as a distinct stage between stages 1 and 3 of AD and to identify those at high risk for clinical progression. In a prospective multicenter study (DELCODE) involving 457 participants across the AD continuum, we analyzed plasma phospho-tau 181 (p181) and neurofilament light chain (NfL) and assessed their association with longitudinal cognition, hippocampal atrophy, and AD clinical stage transition. The results showed that baseline plasma p181 levels were elevated and increased more rapidly in A + SCD individuals compared to amyloid-positive cognitively unimpaired (A + CU) individuals (stage 1). NfL levels rose across A + CU, A + SCD, and amyloid-positive mild cognitive impairment (A + MCI, stage 3). In A + SCD, but not in A + CU, higher p181 levels predicted cognitive decline (PACC5) and transition to MCI. In conclusion, plasma p181 provides molecular biomarker evidence supporting A + SCD as a pre-dementia AD stage (stage 2) distinct from A + CU (stage 1) and helps identify individuals at risk for cognitive decline early in the AD continuum.
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000279379 650_7 $$2NLM Chemicals$$aBiomarkers
000279379 650_7 $$2NLM Chemicals$$aNeurofilament Proteins
000279379 650_7 $$2NLM Chemicals$$aneurofilament protein L
000279379 650_7 $$2NLM Chemicals$$atau Proteins
000279379 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000279379 650_2 $$2MeSH$$aHumans
000279379 650_2 $$2MeSH$$aCognitive Dysfunction: blood
000279379 650_2 $$2MeSH$$aCognitive Dysfunction: diagnosis
000279379 650_2 $$2MeSH$$aCognitive Dysfunction: metabolism
000279379 650_2 $$2MeSH$$aMale
000279379 650_2 $$2MeSH$$aAlzheimer Disease: blood
000279379 650_2 $$2MeSH$$aAlzheimer Disease: metabolism
000279379 650_2 $$2MeSH$$aFemale
000279379 650_2 $$2MeSH$$aBiomarkers: blood
000279379 650_2 $$2MeSH$$aAged
000279379 650_2 $$2MeSH$$aNeurofilament Proteins: blood
000279379 650_2 $$2MeSH$$aDisease Progression
000279379 650_2 $$2MeSH$$atau Proteins: blood
000279379 650_2 $$2MeSH$$aProspective Studies
000279379 650_2 $$2MeSH$$aAged, 80 and over
000279379 650_2 $$2MeSH$$aAmyloid beta-Peptides: blood
000279379 650_2 $$2MeSH$$aUnited States
000279379 650_2 $$2MeSH$$aHippocampus: pathology
000279379 650_2 $$2MeSH$$aLongitudinal Studies
000279379 650_2 $$2MeSH$$aAtrophy
000279379 650_2 $$2MeSH$$aNeuropsychological Tests
000279379 650_2 $$2MeSH$$aCognition: physiology
000279379 650_2 $$2MeSH$$aMiddle Aged
000279379 693__ $$0EXP:(DE-2719)DELCODE-20140101$$5EXP:(DE-2719)DELCODE-20140101$$eLongitudinal Cognitive Impairment and Dementia Study$$x0
000279379 7001_ $$aSoter, Ester$$b1
000279379 7001_ $$aOtt, Julia Maren$$b2
000279379 7001_ $$0P:(DE-2719)9002443$$aWacker, Madeleine$$b3$$udzne
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000279379 7001_ $$0P:(DE-2719)2811024$$aPeters, Oliver$$b5$$udzne
000279379 7001_ $$0P:(DE-2719)9003016$$aHellmann-Regen, Julian David Nicolai$$b6$$udzne
000279379 7001_ $$0P:(DE-2719)9002878$$aSchneider, Luisa-Sophie$$b7
000279379 7001_ $$aWang, Xiao$$b8
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000279379 7001_ $$0P:(DE-2719)2812446$$aSpruth, Eike Jakob$$b10
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000279379 7001_ $$00000-0001-5785-9594$$aHansen, Niels$$b15
000279379 7001_ $$aRostamzadeh, Ayda$$b16
000279379 7001_ $$0P:(DE-2719)2000005$$aDüzel, Emra$$b17$$udzne
000279379 7001_ $$0P:(DE-2719)2811614$$aGlanz, Wenzel$$b18$$udzne
000279379 7001_ $$0P:(DE-2719)9001517$$aIncesoy, Enise I$$b19$$udzne
000279379 7001_ $$0P:(DE-2719)2811351$$aBuerger, Katharina$$b20$$udzne
000279379 7001_ $$0P:(DE-2719)9002557$$aJanowitz, Daniel$$b21$$udzne
000279379 7001_ $$0P:(DE-2719)9000543$$aEwers, Michael$$b22
000279379 7001_ $$0P:(DE-2719)2812234$$aPerneczky, Robert$$b23
000279379 7001_ $$0P:(DE-2719)9001808$$aRauchmann, Boris Stephan$$b24$$udzne
000279379 7001_ $$0P:(DE-2719)2000026$$aTeipel, Stefan$$b25$$udzne
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000279379 7001_ $$0P:(DE-2719)2000055$$aLaske, Christoph$$b27$$udzne
000279379 7001_ $$0P:(DE-2719)9003152$$aSodenkamp, Sebastian$$b28$$udzne
000279379 7001_ $$0P:(DE-2719)2811324$$aSpottke, Annika$$b29$$udzne
000279379 7001_ $$0P:(DE-2719)9002991$$aBrustkern, Johanna$$b30$$udzne
000279379 7001_ $$0P:(DE-2719)2810593$$aBrosseron, Frederic$$b31
000279379 7001_ $$0P:(DE-2719)2000057$$aWagner, Michael$$b32$$udzne
000279379 7001_ $$0P:(DE-2719)9001773$$aStark, Melina$$b33$$udzne
000279379 7001_ $$0P:(DE-2719)2812139$$aKleineidam, Luca$$b34
000279379 7001_ $$0P:(DE-2719)9002519$$aShao, Kai$$b35$$udzne
000279379 7001_ $$0P:(DE-2719)9002520$$aLüsebrink, Falk$$b36$$udzne
000279379 7001_ $$0P:(DE-2719)2812398$$aYakupov, Renat$$b37
000279379 7001_ $$0P:(DE-2719)2811245$$aSchmid, Matthias$$b38$$udzne
000279379 7001_ $$aHetzer, Stefan$$b39
000279379 7001_ $$aDechent, Peter$$b40
000279379 7001_ $$aScheffler, Klaus$$b41
000279379 7001_ $$0P:(DE-2719)2812972$$aBerron, David$$b42
000279379 7001_ $$0P:(DE-2719)2000032$$aJessen, Frank$$b43$$udzne
000279379 7001_ $$0P:(DE-2719)2811275$$aSynofzik, Matthis$$b44
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000279379 773__ $$0PERI:(DE-600)1502531-7$$a10.1038/s41380-025-03021-0$$gVol. 30, no. 7, p. 3150 - 3159$$n7$$p3150 - 3159$$tMolecular psychiatry$$v30$$x1359-4184$$y2025
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