Journal Article

DZNE-2024-00201

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Florbetapir PET-assessed demyelination is associated with faster tau accumulation in an APOE ε4-dependent manner.

Rubinski, A. ; Dewenter, A. ; Zheng, L. ; Franzmeier, N. ; Stephenson, H. ; Deming, Y. ; Duering, M. ; Gesierich, B.Extern* ; Denecke, J. ; Pham, A.-V. ; Bendlin, B. ; Ewers, M. (Last author)DZNE* ; Initiative, A. D. N. (Collaboration Author)

2024
Springer-Verl. Heidelberg [u.a.]

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Please use a persistent id in citations: doi:10.1007/s00259-023-06530-8

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.

Keyword(s): Humans (MeSH) ; Apolipoprotein E4: genetics (MeSH) ; Alzheimer Disease: diagnostic imaging (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Apolipoproteins E (MeSH) ; Brain: metabolism (MeSH) ; Cognitive Dysfunction: metabolism (MeSH) ; Demyelinating Diseases: metabolism (MeSH) ; tau Proteins: metabolism (MeSH) ; Positron-Emission Tomography (MeSH) ; Aniline Compounds (MeSH) ; Ethylene Glycols (MeSH) ; APOE ; Florbetapir-PET ; Myelin ; Tau ; Apolipoprotein E4 ; florbetapir ; Amyloid beta-Peptides ; Apolipoproteins E ; tau Proteins ; Aniline Compounds ; Ethylene Glycols

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Contributing Institute(s):

1. Clinical Research (Munich) (Clinical Research (Munich))

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2024

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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