Longitudinal amyloid and tau accumulation in autosomal dominant Alzheimer’s disease: findings from the Colombia-Boston (COLBOS) biomarker study

ABSTRACT: Background: Neuroimaging studies of autosomal dominant Alzheimer's disease (ADAD) enable characterization of the trajectories of cerebral amyloid-β (Aβ) and tau accumulation in the decades prior to clinical symptom onset. Longitudinal rates of regional tau accumulation measured with positron emission tomography (PET) and their relationship with other biomarker and cognitive changes remain to be fully characterized in ADAD. Methods: Fourteen ADAD mutation carriers (Presenilin-1 E280A) and 15 age-matched non-carriers from the Colombian kindred underwent 2-3 sessions of Aβ (11C-Pittsburgh compound B) and tau (18F-flortaucipir) PET, structural magnetic resonance imaging, and neuropsychological evaluation over a 2-4-year follow-up period. Annualized rates of change for imaging and cognitive variables were compared between carriers and non-carriers, and relationships among baseline measurements and rates of change were assessed within carriers. Results: Longitudinal measurements were consistent with a sequence of ADAD-related changes beginning with Aβ accumulation (16 years prior to expected symptom onset, EYO), followed by entorhinal cortex (EC) tau (9 EYO), neocortical tau (6 EYO), hippocampal atrophy (6 EYO), and cognitive decline (4 EYO). Rates of tau accumulation among carriers were most rapid in parietal neocortex (~ 9%/year). EC tau PET signal at baseline was a significant predictor of subsequent neocortical tau accumulation and cognitive decline within carriers. Conclusions: Our results are consistent with the sequence of biological changes in ADAD implied by cross-sectional studies and highlight the importance of EC tau as an early biomarker and a potential link between Aβ burden and neocortical tau accumulation in ADAD. Keywords: Alzheimer’s; Amyloid; Autosomal-Dominant; Imaging; Longitudinal; Tau.

• Autores: Ramos Pérez, Claudia Patricia; Lopera Restrepo, Francisco Javier; Quiroz Gaviria, Yakeel Tatiana; Sánchez, Justin S.; Hanseeuw, Bernard J.; Sperling, Reisa A.; Baena Pineda, Ana Yulied; Bocanegra, Yamile; Aguillón Niño, David Fernando; Guzmán Vélez, Edmarie; Pardilla Delgado, Enmanuelle; Ramírez Gómez, Liliana; Vila Castelar, Clara; Martínez, Jairo; Fox Fuller, Joshua T.; Ochoa Escudero, Martin; Álvarez, Sergio; Jacobs, Heidi I. L.; Schultz, Aaron P.; Gatchel, Jennifer R.; Becker, J Alex; Katz, Samantha R.; Mayblyum, Danielle V.; Price, Julie C.; Reiman, Eric M.; Johnson, Keith A.
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2021
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/43058
• Acceso en línea: https://hdl.handle.net/10495/43058
• Palabra clave: Alzheimer Disease; Enfermedad de Alzheimer; Amyloid beta-Peptides; Péptidos beta-Amiloides; Biomarkers; Biomarcadores; Cross-Sectional Studies; Estudios Transversales; Magnetic Resonance Imaging; Imagen por Resonancia Magnética; Positron-Emission Tomography; Tomografía de Emisión de Positrones; tau Proteins; Proteínas tau; https://id.nlm.nih.gov/mesh/D000544; https://id.nlm.nih.gov/mesh/D016229; https://id.nlm.nih.gov/mesh/D015415; https://id.nlm.nih.gov/mesh/D003430; https://id.nlm.nih.gov/mesh/D008279; https://id.nlm.nih.gov/mesh/D049268; https://id.nlm.nih.gov/mesh/D016875
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/2.5/co/