PET in preclinical AD: image harmonization, characterization of the centiloid metric of Aβ load and associations with tau fluid biomarkers

This thesis explores technical factors influencing brain PET quantification, developing brain PET harmonization framework, assessing Centiloid robustness as a clinical biomarker, and evaluating the associations between fluid biomarkers and amyloid and tau PET imaging in the early stage of preclinica...

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Detalles Bibliográficos
Autor: Shekari, Mahnaz
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/690636
Acceso en línea:http://hdl.handle.net/10803/690636
Access Level:acceso abierto
Palabra clave:Preclinical Alzheimer’s Disease
Fluid biomarkers
PET
Harmonization
Enfermedad de Alzheimer Preclínica
Biomarcadores en Fluidos
Harmonización
Malaltia d'Alzheimer Preclínica
Biomarcadors en Fluids
Harmonització
616.8
Descripción
Sumario:This thesis explores technical factors influencing brain PET quantification, developing brain PET harmonization framework, assessing Centiloid robustness as a clinical biomarker, and evaluating the associations between fluid biomarkers and amyloid and tau PET imaging in the early stage of preclinical AD. Findings support prospective and retrospective harmonization using the developed framework, soon to be EARL accreditation's new harmonization criteria for brain PET imaging. Centiloid metric showed to be a robust metric, that can be used as a reliable biomarker. Additionally, promising results from CSF and blood biomarker studies, notably new blood biomarkers (blood ptau231 and ptau217), revealed their predictive abilities of for amyloid progression and moderate correlations with tau PET signals. This underscores their potential as valuable tools for cohort enrichment and recruitment of clinical trials. The thesis's outcomes contribute to the EARL accreditation program's first brain PET harmonization guideline, EMA approval for Centiloid use in clinical routine studies, and improving the understanding of new blood biomarkers and their application in preclinical AD.