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000268319 1001_ $$aRubinski, Anna$$b0
000268319 245__ $$aFlorbetapir PET-assessed demyelination is associated with faster tau accumulation in an APOE ε4-dependent manner.
000268319 260__ $$aHeidelberg [u.a.]$$bSpringer-Verl.$$c2024
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000268319 520__ $$aThe main objectives were to test whether (1) a decrease in myelin is associated with enhanced rate of fibrillar tau accumulation and cognitive decline in Alzheimer's disease, and (2) whether apolipoprotein E (APOE) ε4 genotype is associated with worse myelin decrease and thus tau accumulation.To address our objectives, we repurposed florbetapir-PET as a marker of myelin in the white matter (WM) based on previous validation studies showing that beta-amyloid (Aβ) PET tracers bind to WM myelin. We assessed 43 Aβ-biomarker negative (Aβ-) cognitively normal participants and 108 Aβ+ participants within the AD spectrum with florbetapir-PET at baseline and longitudinal flortaucipir-PET as a measure of fibrillar tau (tau-PET) over ~ 2 years. In linear regression analyses, we tested florbetapir-PET in the whole WM and major fiber tracts as predictors of tau-PET accumulation in a priori defined regions of interest (ROIs) and fiber-tract projection areas. In mediation analyses we tested whether tau-PET accumulation mediates the effect of florbetapir-PET in the whole WM on cognition. Finally, we assessed the role of myelin alteration on the association between APOE and tau-PET accumulation.Lower florbetapir-PET in the whole WM or at a given fiber tract was predictive of faster tau-PET accumulation in Braak stages or the connected grey matter areas in Aβ+ participants. Faster tau-PET accumulation in higher cortical brain areas mediated the association between a decrease in florbetapir-PET in the WM and a faster rate of decline in global cognition and episodic memory. APOE ε4 genotype was associated with a worse decrease in the whole WM florbetapir-PET and thus enhanced tau-PET accumulation.Myelin alterations are associated in an APOE ε4 dependent manner with faster tau progression and cognitive decline, and may therefore play a role in the etiology of AD.
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000268319 650_7 $$2Other$$aAPOE
000268319 650_7 $$2Other$$aFlorbetapir-PET
000268319 650_7 $$2Other$$aMyelin
000268319 650_7 $$2Other$$aTau
000268319 650_7 $$2NLM Chemicals$$aApolipoprotein E4
000268319 650_7 $$06867Q6IKOD$$2NLM Chemicals$$aflorbetapir
000268319 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000268319 650_7 $$2NLM Chemicals$$aApolipoproteins E
000268319 650_7 $$2NLM Chemicals$$atau Proteins
000268319 650_7 $$2NLM Chemicals$$aAniline Compounds
000268319 650_7 $$2NLM Chemicals$$aEthylene Glycols
000268319 650_2 $$2MeSH$$aHumans
000268319 650_2 $$2MeSH$$aApolipoprotein E4: genetics
000268319 650_2 $$2MeSH$$aAlzheimer Disease: diagnostic imaging
000268319 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000268319 650_2 $$2MeSH$$aAlzheimer Disease: metabolism
000268319 650_2 $$2MeSH$$aAmyloid beta-Peptides: metabolism
000268319 650_2 $$2MeSH$$aApolipoproteins E
000268319 650_2 $$2MeSH$$aBrain: metabolism
000268319 650_2 $$2MeSH$$aCognitive Dysfunction: metabolism
000268319 650_2 $$2MeSH$$aDemyelinating Diseases: metabolism
000268319 650_2 $$2MeSH$$atau Proteins: metabolism
000268319 650_2 $$2MeSH$$aPositron-Emission Tomography
000268319 650_2 $$2MeSH$$aAniline Compounds
000268319 650_2 $$2MeSH$$aEthylene Glycols
000268319 7001_ $$aDewenter, Anna$$b1
000268319 7001_ $$aZheng, Lukai$$b2
000268319 7001_ $$aFranzmeier, Nicolai$$b3
000268319 7001_ $$aStephenson, Henry$$b4
000268319 7001_ $$aDeming, Yuetiva$$b5
000268319 7001_ $$aDuering, Marco$$b6
000268319 7001_ $$0P:(DE-2719)9001112$$aGesierich, Benno$$b7$$udzne
000268319 7001_ $$aDenecke, Jannis$$b8
000268319 7001_ $$0P:(DE-HGF)0$$aPham, An-Vi$$b9
000268319 7001_ $$aBendlin, Barbara$$b10
000268319 7001_ $$0P:(DE-2719)9000543$$aEwers, Michael$$b11$$eLast author$$udzne
000268319 7001_ $$aInitiative, Alzheimer’s Disease Neuroimaging$$b12$$eCollaboration Author
000268319 773__ $$0PERI:(DE-600)2098375-X$$a10.1007/s00259-023-06530-8$$gVol. 51, no. 4, p. 1035 - 1049$$n4$$p1035 - 1049$$tEuropean journal of nuclear medicine and molecular imaging$$v51$$x1619-7070$$y2024
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