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000283155 1001_ $$aKinton, Sofia$$b0
000283155 1112_ $$aAlzheimer’s Association International Conference$$cToronto$$d2025-07-27 - 2025-07-31$$gAAIC 25$$wCanada
000283155 245__ $$aProteomic Profiling of CSF Reveals Inflammatory Pathways Associated with Tau Neuropathology in Alzheimer's Disease
000283155 260__ $$c2025
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000283155 520__ $$aAggregation of amyloid beta (Aβ) and tau proteins is a hallmark of Alzheimer's disease (AD) and tauopathies. In AD, extracellular deposition of Aβ peptide precedes tau aggregation and the onset of neuroinflammatory processes. Both neuroinflammation and tau deposition are associated with synaptic loss, neurodegeneration, and cognitive decline. However, the precise sequence of events from amyloid deposition to tau aggregation, neuroinflammation, and neurodegeneration remains unclear. A cross-sectional analysis of tau and other proteins in the cerebrospinal fluid (CSF) of AD patients can provide insight into the inflammatory and degenerative processes. Tau levels may be used as a proxy for disease progression, and we hypothesize that the expression of neuroinflammatory markers will be modulated in response to increasing tau aggregation.To investigate this, we collaborated with the EPND-biomarker consortium to analyze over 150 human CSF samples from AD and control patients. We measured levels of Aβ1-40, Aβ1-42, pTau181, and total tau, and conducted proteomic profiling using the O-link and SomaScan platforms. Next, AD patients were stratified into Aβ+Tau+ and Aβ+Tau- groups to identify biomarkers associated with Aβ and/or tau aggregation.As expected, inflammation markers were elevated in AD CSF samples compared to controls. Interestingly, we observed distinct correlations between these markers and amyloid versus tau pathology biomarkers. Approximately 10% of the measured CSF proteins (∼250 proteins) showed significant differences (p < 0.05) between AD and control samples. CSF samples with elevated tau levels exhibited altered levels of proteins involved in the complement cascade, cytokine-cytokine receptor interactions, cell adhesion, and vesicular transport.Increased inflammation markers were observed in AD. Proteins linked to innate immune response and synaptic loss were significantly altered in relation to tau aggregation. These findings are crucial for guiding therapeutic strategies for neurodegenerative diseases and assessing their efficacy.
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000283155 650_7 $$2NLM Chemicals$$aBiomarkers
000283155 650_7 $$2NLM Chemicals$$atau Proteins
000283155 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000283155 650_7 $$2NLM Chemicals$$aPeptide Fragments
000283155 650_2 $$2MeSH$$aHumans
000283155 650_2 $$2MeSH$$aBiomarkers: cerebrospinal fluid
000283155 650_2 $$2MeSH$$aAlzheimer Disease: cerebrospinal fluid
000283155 650_2 $$2MeSH$$atau Proteins: cerebrospinal fluid
000283155 650_2 $$2MeSH$$aAmyloid beta-Peptides: cerebrospinal fluid
000283155 650_2 $$2MeSH$$aFemale
000283155 650_2 $$2MeSH$$aMale
000283155 650_2 $$2MeSH$$aAged
000283155 650_2 $$2MeSH$$aCross-Sectional Studies
000283155 650_2 $$2MeSH$$aProteomics
000283155 650_2 $$2MeSH$$aMiddle Aged
000283155 650_2 $$2MeSH$$aPeptide Fragments: cerebrospinal fluid
000283155 7001_ $$aDujardin, Simon$$b1
000283155 7001_ $$aLevit, Mikhail$$b2
000283155 7001_ $$aPao, Ping-Chieh$$b3
000283155 7001_ $$aSardi, Pablo$$b4
000283155 7001_ $$aZhang, Bailin$$b5
000283155 7001_ $$aDodge, James$$b6
000283155 7001_ $$aKrishnan, Rajaraman$$b7
000283155 7001_ $$aRizzo, Marianna$$b8
000283155 7001_ $$aTeunissen, Charlotte E$$b9
000283155 7001_ $$aZetterberg, Henrik$$b10
000283155 7001_ $$aBlennow, Kaj$$b11
000283155 7001_ $$aKollmorgen, Gwendlyn$$b12
000283155 7001_ $$aRamia, Nancy$$b13
000283155 7001_ $$aFernandes, Sara B Gomes$$b14
000283155 7001_ $$aKrüger, Rejko$$b15
000283155 7001_ $$aBorejko, Olga$$b16
000283155 7001_ $$aAarsland, Dag$$b17
000283155 7001_ $$aHu, Michele$$b18
000283155 7001_ $$0P:(DE-2719)2810314$$aKlockgether, Thomas$$b19$$udzne
000283155 7001_ $$0P:(DE-2719)2811916$$aBrockmann, Kathrin$$b20$$udzne
000283155 7001_ $$0P:(DE-2719)2320009$$aGasser, Thomas$$b21$$udzne
000283155 7001_ $$0P:(DE-2719)2000032$$aJessen, Frank$$b22$$udzne
000283155 7001_ $$0P:(DE-2719)2811324$$aSpottke, Annika$$b23$$udzne
000283155 7001_ $$avan der Flier, Wiesje M$$b24
000283155 7001_ $$aLemstra, Afina W$$b25
000283155 7001_ $$aTijms, Betty M$$b26
000283155 7001_ $$aFrisoni, Giovanni B$$b27
000283155 7001_ $$aHort, Jakub$$b28
000283155 7001_ $$aNedelska, Zuzana$$b29
000283155 7001_ $$aChevalier, Claire$$b30
000283155 7001_ $$aVisser, Pieter Jelle$$b31
000283155 7001_ $$aVos, Stephanie J B$$b32
000283155 773__ $$0PERI:(DE-600)2201940-6$$a10.1002/alz70856_106780$$gVol. 21 Suppl 2, no. S2, p. e106780$$nS2$$pe106780$$tAlzheimer's and dementia$$v21$$x1552-5260$$y2025
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