Tau and Amyloid Pet Imaging in a Colombian Kindred with Autosomal-Dominant Alzheimer's Disease

Background: Examining rare families with autosomal dominant mutations that cause early-onset Alzheimer's disease (AD) provides a unique model for studying the trajectory of AD-related pathology, especially in the preclinical stages. We used PET imaging to characterize the relation between amyloid burden and tau accumulation in the brains of young, asymptomatic PSEN1 E280A mutation carriers and non- carriers from a Colombian kindred with autosomal dominant AD (ADAD). We hypothesized that in this sample, cortical amyloid pathology precedes tau tangle formation both within and beyond the medial temporal lobe. Methods: Six cognitively-unimpaired carriers of the PSEN1 mutation (mean age 32 years) and six non- carriers (mean age 36 years) traveled to Boston for tau and amyloid imaging. [C11] PIB PET cerebral-to- cerebellar DVRs and [F18] T807-PET cerebral-to-cerebellar SUVRs were compared based on mutation status. Both PiB and T807 utilized structural ROIs as defined by Freesurfer. Groups were matched for age, sex, education level, and neuropsychological test performance. Results: Compared with non-carriers, cognitively unimpaired mutation carriers had significantly higher mean cortical PIB DVRs (carriers: 1.16 +/-0.06, non-carriers: 1.05 +/-0.02, p<0.001). The group differences for T807 SUVRs were in the expected direction but were non-significant (inferior temporal lobe regions; carriers: 1.15 +/-0.12, non-carriers: 1.13 +/-0.06, p= 0.74; entorhinal cortex; carriers: 1.21 +/-0.40, non- carriers: 1.02 +/-0.06, p= 0.28). There was also a trending association between amyloid burden and T807 binding in entorhinal cortex (r= 0.57, p=0.07), which was in part driven by the oldest mutation carrier in this sample (age 38), who was still several years away from usual clinical onset at age 44. Enrollment is ongoing; additional subjects will be imaged over the coming months. Conclusions: Initial findings from this ongoing study are consistent with the hypothesis that mutation carriers express amyloid deposition before tau deposition. Studying amyloid and tau concomitantly in ADAD is a promising method for clarifying the temporal relationship between the emergence of tau and amyloid pathology.

• Autores: Lopera Restrepo, Francisco Javier; Baena, Ana; Quiroz, Yakeel T.; Sperling, Reisa A.; Arboleda Velasquez, Joseph; Schultz, Aaron P.; Cosio, Danielle M.; LaPoint, Molly R.; Judge, Kelly; Jaimes, Sehily Y.; Norton, Daniel J.; Reiman, Eric M.; Johnson, Keith
• Tipo de recurso: http://purl.org/coar/resource_type/R60J-J5BD
• Fecha de publicación: 2016
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/47820
• Acceso en línea: https://hdl.handle.net/10495/47820
• Palabra clave: 610 - Medicina y salud; Enfermedad de Alzheimer; Alzheimer Disease; Tomografía de Emisión de Positrones; Positron-Emission Tomography; https://id.nlm.nih.gov/mesh/D000544; https://id.nlm.nih.gov/mesh/D049268; ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
• Rights: openAccess
• License: http://creativecommons.org/licenses/by-nc-nd/4.0/