%0 Journal Article
%A Rubinski, Anna
%A Dewenter, Anna
%A Zheng, Lukai
%A Franzmeier, Nicolai
%A Stephenson, Henry
%A Deming, Yuetiva
%A Duering, Marco
%A Gesierich, Benno
%A Denecke, Jannis
%A Pham, An-Vi
%A Bendlin, Barbara
%A Ewers, Michael
%T Florbetapir PET-assessed demyelination is associated with faster tau accumulation in an APOE ε4-dependent manner.
%J European journal of nuclear medicine and molecular imaging
%V 51
%N 4
%@ 1619-7070
%C Heidelberg [u.a.]
%I Springer-Verl.
%M DZNE-2024-00201
%P 1035 - 1049
%D 2024
%X The 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.
%K Humans
%K Apolipoprotein E4: genetics
%K Alzheimer Disease: diagnostic imaging
%K Alzheimer Disease: genetics
%K Alzheimer Disease: metabolism
%K Amyloid beta-Peptides: metabolism
%K Apolipoproteins E
%K Brain: metabolism
%K Cognitive Dysfunction: metabolism
%K Demyelinating Diseases: metabolism
%K tau Proteins: metabolism
%K Positron-Emission Tomography
%K Aniline Compounds
%K Ethylene Glycols
%K APOE (Other)
%K Florbetapir-PET (Other)
%K Myelin (Other)
%K Tau (Other)
%K Apolipoprotein E4 (NLM Chemicals)
%K florbetapir (NLM Chemicals)
%K Amyloid beta-Peptides (NLM Chemicals)
%K Apolipoproteins E (NLM Chemicals)
%K tau Proteins (NLM Chemicals)
%K Aniline Compounds (NLM Chemicals)
%K Ethylene Glycols (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%2 pmc:PMC10881623
%$ pmid:38049659
%R 10.1007/s00259-023-06530-8
%U https://pub.dzne.de/record/268319