TY  - JOUR
AU  - Rubinski, Anna
AU  - Dewenter, Anna
AU  - Zheng, Lukai
AU  - Franzmeier, Nicolai
AU  - Stephenson, Henry
AU  - Deming, Yuetiva
AU  - Duering, Marco
AU  - Gesierich, Benno
AU  - Denecke, Jannis
AU  - Pham, An-Vi
AU  - Bendlin, Barbara
AU  - Ewers, Michael
TI  - Florbetapir PET-assessed demyelination is associated with faster tau accumulation in an APOE ε4-dependent manner.
JO  - European journal of nuclear medicine and molecular imaging
VL  - 51
IS  - 4
SN  - 1619-7070
CY  - Heidelberg [u.a.]
PB  - Springer-Verl.
M1  - DZNE-2024-00201
SP  - 1035 - 1049
PY  - 2024
AB  - 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.
KW  - Humans
KW  - Apolipoprotein E4: genetics
KW  - Alzheimer Disease: diagnostic imaging
KW  - Alzheimer Disease: genetics
KW  - Alzheimer Disease: metabolism
KW  - Amyloid beta-Peptides: metabolism
KW  - Apolipoproteins E
KW  - Brain: metabolism
KW  - Cognitive Dysfunction: metabolism
KW  - Demyelinating Diseases: metabolism
KW  - tau Proteins: metabolism
KW  - Positron-Emission Tomography
KW  - Aniline Compounds
KW  - Ethylene Glycols
KW  - APOE (Other)
KW  - Florbetapir-PET (Other)
KW  - Myelin (Other)
KW  - Tau (Other)
KW  - Apolipoprotein E4 (NLM Chemicals)
KW  - florbetapir (NLM Chemicals)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Apolipoproteins E (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
KW  - Aniline Compounds (NLM Chemicals)
KW  - Ethylene Glycols (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC10881623
C6  - pmid:38049659
DO  - DOI:10.1007/s00259-023-06530-8
UR  - https://pub.dzne.de/record/268319
ER  -