Florbetapir PET-assessed demyelination is associated with faster tau accumulation in an APOE ε4-dependent manner.
Eur J Nucl Med Mol Imaging
; 51(4): 1035-1049, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38049659
ABSTRACT
PURPOSE:
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.METHODS:
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 (Aß) PET tracers bind to WM myelin. We assessed 43 Aß-biomarker negative (Aß-) cognitively normal participants and 108 Aß+ 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.RESULTS:
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 Aß+ 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.CONCLUSION:
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Doenças Desmielinizantes
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Etilenoglicóis
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Doença de Alzheimer
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Disfunção Cognitiva
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Compostos de Anilina
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article