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000278922 0247_ $$2ISSN$$a1552-5279
000278922 037__ $$aDZNE-2025-00648
000278922 041__ $$aEnglish
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000278922 1001_ $$aLiu, Haiyan$$b0
000278922 245__ $$aUbiquitin-proteasome system in the different stages of dominantly inherited Alzheimer's disease.
000278922 260__ $$aHoboken, NJ$$bWiley$$c2025
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000278922 520__ $$aThis study investigated the role of the ubiquitin-proteasome system (UPS) in dominantly inherited Alzheimer's disease (DIAD) by examining cerebrospinal fluid (CSF) levels of UPS proteins.The SOMAscan assay was used to detect changes in UPS proteins in mutation carriers (MCs) relative to disease progression; imaging and CSF biomarkers of amyloid, tau, and neurodegeneration measures; and Clinical Dementia Rating scale.Subtle increases in specific ubiquitin enzymes were detected in MCs up to two decades before symptom onset, with more pronounced elevations in UPS-activating enzymes near symptom onset. Significant correlations were found between UPS proteins and Alzheimer's disease (AD) biomarkers, especially between autophagy markers and late-stage tau biomarkers, microglia, and axonal degeneration.The rise in UPS proteins alongside tau-related markers suggests UPS involvement in tau neurofibrillary tangles. Elevated CSF UPS proteins in DIAD MCs may serve as indicators of disease progression, and may support the UPS as a therapeutic target in AD.This study investigates the ubiquitin-proteasome system (UPS) in Dominantly Inherited Alzheimer's Disease (DIAD), highlighting early molecular changes linked to disease progression. Using SOMAscan proteomics, we identified significant UPS protein alterations in cerebrospinal fluid of mutation carriers, notably up to 20 years before clinical symptom onset. Correlations between UPS protein levels and Alzheimer's biomarkers, particularly tau and neurodegeneration markers, suggest a strong association between UPS dysregulation and tau pathology in DIAD. Dynamic UPS changes align with A/T biological staging: UPS proteins were shown to increase across Aβ/tau (A/T) groups, with largest increases in the A+/T+ group, reinforcing their role in late-stage tau pathology and disease progression. These findings underscore the potential of UPS proteins as early biomarkers for Alzheimer's disease progression and as novel therapeutic targets, especially in tau-pathology-driven neurodegeneration. This work contributes to understanding AD pathogenesis, by emphasizing the importance of protein quality control systems and by offering avenues for future biomarker discovery and therapeutic development in Alzheimer's disease.
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000278922 650_7 $$2Other$$aamyloid beta
000278922 650_7 $$2Other$$aamyloid precursor protein
000278922 650_7 $$2Other$$aautophagy–lysosome pathway
000278922 650_7 $$2Other$$abiomarker discovery
000278922 650_7 $$2Other$$adominantly inherited Alzheimer's disease
000278922 650_7 $$2Other$$agenetic mutations
000278922 650_7 $$2Other$$aneurodegeneration
000278922 650_7 $$2Other$$apresenilin 1
000278922 650_7 $$2Other$$apresenilin 2
000278922 650_7 $$2Other$$aprotein aggregation
000278922 650_7 $$2Other$$aprotein degradation
000278922 650_7 $$2Other$$aproteomic analysis
000278922 650_7 $$2Other$$aproteostasis
000278922 650_7 $$2Other$$atau pathology
000278922 650_7 $$2Other$$aubiquitin–proteasome system
000278922 650_7 $$2NLM Chemicals$$aUbiquitin
000278922 650_7 $$0EC 3.4.25.1$$2NLM Chemicals$$aProteasome Endopeptidase Complex
000278922 650_7 $$2NLM Chemicals$$aBiomarkers
000278922 650_7 $$2NLM Chemicals$$atau Proteins
000278922 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000278922 650_2 $$2MeSH$$aHumans
000278922 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000278922 650_2 $$2MeSH$$aAlzheimer Disease: cerebrospinal fluid
000278922 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000278922 650_2 $$2MeSH$$aUbiquitin: cerebrospinal fluid
000278922 650_2 $$2MeSH$$aProteasome Endopeptidase Complex: cerebrospinal fluid
000278922 650_2 $$2MeSH$$aProteasome Endopeptidase Complex: metabolism
000278922 650_2 $$2MeSH$$aFemale
000278922 650_2 $$2MeSH$$aMale
000278922 650_2 $$2MeSH$$aBiomarkers: cerebrospinal fluid
000278922 650_2 $$2MeSH$$atau Proteins: cerebrospinal fluid
000278922 650_2 $$2MeSH$$aDisease Progression
000278922 650_2 $$2MeSH$$aMiddle Aged
000278922 650_2 $$2MeSH$$aAged
000278922 650_2 $$2MeSH$$aMutation: genetics
000278922 650_2 $$2MeSH$$aAmyloid beta-Peptides: cerebrospinal fluid
000278922 650_2 $$2MeSH$$aAdult
000278922 7001_ $$aBui, Quoc$$b1
000278922 7001_ $$aHassenstab, Jason$$b2
000278922 7001_ $$aGordon, Brian A$$b3
000278922 7001_ $$aBenzinger, Tammie L S$$b4
000278922 7001_ $$aTimsina, Jigyasha$$b5
000278922 7001_ $$aSung, Yun Ju$$b6
000278922 7001_ $$aKarch, Celeste$$b7
000278922 7001_ $$aRenton, Alan E$$b8
000278922 7001_ $$aDaniels, Alisha$$b9
000278922 7001_ $$aMorris, John C$$b10
000278922 7001_ $$aXiong, Chengjie$$b11
000278922 7001_ $$aIbanez, Laura$$b12
000278922 7001_ $$aPerrin, Richard J$$b13
000278922 7001_ $$aLlibre-Guerra, Jorge J$$b14
000278922 7001_ $$aDay, Gregory S$$b15
000278922 7001_ $$aSupnet-Bell, Charlene$$b16
000278922 7001_ $$aXu, Xiong$$b17
000278922 7001_ $$aBerman, Sarah B$$b18
000278922 7001_ $$aChhatwal, Jasmeer P$$b19
000278922 7001_ $$aIkeuchi, Takeshi$$b20
000278922 7001_ $$aKasuga, Kensaku$$b21
000278922 7001_ $$aNiimi, Yoshiki$$b22
000278922 7001_ $$aHuey, Edward D$$b23
000278922 7001_ $$aSchofield, Peter R$$b24
000278922 7001_ $$aBrooks, William S$$b25
000278922 7001_ $$aRyan, Natalie S$$b26
000278922 7001_ $$0P:(DE-2719)2000010$$aJucker, Mathias$$b27$$udzne
000278922 7001_ $$0P:(DE-2719)2000055$$aLaske, Christoph$$b28$$udzne
000278922 7001_ $$0P:(DE-2719)2811659$$aLevin, Johannes$$b29$$udzne
000278922 7001_ $$0P:(DE-2719)2811820$$aVöglein, Jonathan$$b30$$udzne
000278922 7001_ $$aRoh, Jee Hoon$$b31
000278922 7001_ $$aLopera, Francisco$$b32
000278922 7001_ $$aBateman, Randall J$$b33
000278922 7001_ $$aCruchaga, Carlos$$b34
000278922 7001_ $$00000-0002-6764-3866$$aMcDade, Eric M$$b35
000278922 7001_ $$ateam, For DIAN study$$b36$$eCollaboration Author
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