% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Rubinski:268319,
author = {Rubinski, Anna and Dewenter, Anna and Zheng, Lukai and
Franzmeier, Nicolai and Stephenson, Henry and Deming,
Yuetiva and Duering, Marco and Gesierich, Benno and Denecke,
Jannis and Pham, An-Vi and Bendlin, Barbara and Ewers,
Michael},
collaboration = {Initiative, Alzheimer’s Disease Neuroimaging},
title = {{F}lorbetapir {PET}-assessed demyelination is associated
with faster tau accumulation in an {APOE} ε4-dependent
manner.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {51},
number = {4},
issn = {1619-7070},
address = {Heidelberg [u.a.]},
publisher = {Springer-Verl.},
reportid = {DZNE-2024-00201},
pages = {1035 - 1049},
year = {2024},
abstract = {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.},
keywords = {Humans / Apolipoprotein E4: genetics / Alzheimer Disease:
diagnostic imaging / Alzheimer Disease: genetics / Alzheimer
Disease: metabolism / Amyloid beta-Peptides: metabolism /
Apolipoproteins E / Brain: metabolism / Cognitive
Dysfunction: metabolism / Demyelinating Diseases: metabolism
/ tau Proteins: metabolism / Positron-Emission Tomography /
Aniline Compounds / Ethylene Glycols / APOE (Other) /
Florbetapir-PET (Other) / Myelin (Other) / Tau (Other) /
Apolipoprotein E4 (NLM Chemicals) / florbetapir (NLM
Chemicals) / Amyloid beta-Peptides (NLM Chemicals) /
Apolipoproteins E (NLM Chemicals) / tau Proteins (NLM
Chemicals) / Aniline Compounds (NLM Chemicals) / Ethylene
Glycols (NLM Chemicals)},
cin = {Clinical Research (Munich)},
ddc = {610},
cid = {I:(DE-2719)1111015},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC10881623},
pubmed = {pmid:38049659},
doi = {10.1007/s00259-023-06530-8},
url = {https://pub.dzne.de/record/268319},
}