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000274024 041__ $$aEnglish
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000274024 1001_ $$aMravinacová, Sára$$b0
000274024 245__ $$aAddressing inter individual variability in CSF levels of brain derived proteins across neurodegenerative diseases.
000274024 260__ $$a[London]$$bMacmillan Publishers Limited, part of Springer Nature$$c2025
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000274024 520__ $$aAccurate diagnosis and monitoring of neurodegenerative diseases require reliable biomarkers. Cerebrospinal fluid (CSF) proteins are promising candidates for reflecting brain pathology; however, their diagnostic utility may be compromised by natural variability between individuals, weakening their association with disease. Here, we measured the levels of 69 pre-selected proteins in cerebrospinal fluid using antibody-based suspension bead array technology in a multi-disease cohort of 499 individuals with neurodegenerative disorders including Alzheimer's disease (AD), behavioral variant frontotemporal dementia, primary progressive aphasias, amyotrophic lateral sclerosis (ALS), corticobasal syndrome, primary supranuclear palsy, along with healthy controls. We identify significant inter-individual variability in overall CSF levels of brain-derived proteins, which could not be attributed to specific disease associations. Using linear modelling, we show that adjusting for median CSF levels of brain-derived proteins increases the diagnostic accuracy of proteins previously identified as altered in CSF in the context of neurodegenerative disorders. We further demonstrate a simplified approach for the adjustment using pairs of correlated proteins with opposite alteration in the diseases. With this approach, the proteins adjust for each other and further increase the biomarker performance through additive effect. When comparing the diseases, two proteins-neurofilament medium and myelin basic protein-showed increased levels in ALS compared to other diseases, and neurogranin showed a specific increase in AD. Several other proteins showed similar trends across the studied diseases, indicating that these proteins likely reflect shared processes related to neurodegeneration. Overall, our findings suggest that accounting for inter-individual variability is crucial in future studies to improve the identification and performance of relevant biomarkers. Importantly, we highlight the need for multi-disease studies to identify disease-specific biomarkers.
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000274024 650_7 $$2Other$$aAffinity proteomics
000274024 650_7 $$2Other$$aBiomarker
000274024 650_7 $$2Other$$aCerebrospinal fluid
000274024 650_7 $$2Other$$aInter-individual variability
000274024 650_7 $$2Other$$aMulti-disease
000274024 650_7 $$2Other$$aNeurodegeneration
000274024 650_7 $$2NLM Chemicals$$aBiomarkers
000274024 650_7 $$2NLM Chemicals$$aCerebrospinal Fluid Proteins
000274024 650_2 $$2MeSH$$aHumans
000274024 650_2 $$2MeSH$$aNeurodegenerative Diseases: cerebrospinal fluid
000274024 650_2 $$2MeSH$$aNeurodegenerative Diseases: diagnosis
000274024 650_2 $$2MeSH$$aBiomarkers: cerebrospinal fluid
000274024 650_2 $$2MeSH$$aMale
000274024 650_2 $$2MeSH$$aFemale
000274024 650_2 $$2MeSH$$aAged
000274024 650_2 $$2MeSH$$aMiddle Aged
000274024 650_2 $$2MeSH$$aBrain: metabolism
000274024 650_2 $$2MeSH$$aBrain: pathology
000274024 650_2 $$2MeSH$$aAlzheimer Disease: cerebrospinal fluid
000274024 650_2 $$2MeSH$$aAlzheimer Disease: diagnosis
000274024 650_2 $$2MeSH$$aCerebrospinal Fluid Proteins: analysis
000274024 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: cerebrospinal fluid
000274024 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: diagnosis
000274024 7001_ $$aBergström, Sofia$$b1
000274024 7001_ $$aOlofsson, Jennie$$b2
000274024 7001_ $$ade San José, Nerea Gómez$$b3
000274024 7001_ $$aAnderl-Straub, Sarah$$b4
000274024 7001_ $$aDiehl-Schmid, Janine$$b5
000274024 7001_ $$aFassbender, Klaus$$b6
000274024 7001_ $$0P:(DE-2719)2811326$$aFliessbach, Klaus$$b7$$udzne
000274024 7001_ $$aJahn, Holger$$b8
000274024 7001_ $$aKornhuber, Johannes$$b9
000274024 7001_ $$0P:(DE-2719)9003425$$aLandwehrmeyer, Georg Bernhard$$b10$$udzne
000274024 7001_ $$aLauer, Martin$$b11
000274024 7001_ $$0P:(DE-2719)2811659$$aLevin, Johannes$$b12$$udzne
000274024 7001_ $$0P:(DE-2719)2812633$$aLudolph, Albert C$$b13$$udzne
000274024 7001_ $$0P:(DE-2719)2380559$$aPrudlo, Johannes$$b14$$udzne
000274024 7001_ $$0P:(DE-2719)2812035$$aSchneider, Anja$$b15$$udzne
000274024 7001_ $$aSchroeter, Matthias L$$b16
000274024 7001_ $$0P:(DE-2719)2811317$$aWiltfang, Jens$$b17$$udzne
000274024 7001_ $$aSteinacker, Petra$$b18
000274024 7001_ $$aConsortium, FTLD$$b19$$eCollaboration Author
000274024 7001_ $$aOtto, Markus$$b20
000274024 7001_ $$aNilsson, Peter$$b21
000274024 7001_ $$aMånberg, Anna$$b22
000274024 773__ $$0PERI:(DE-600)2615211-3$$a10.1038/s41598-024-83281-y$$gVol. 15, no. 1, p. 668$$n1$$p668$$tScientific reports$$v15$$x2045-2322$$y2025
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