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PET evidence of preclinical cerebellar amyloid plaque deposition in autosomal dominant Alzheimer’s disease-causing Presenilin-1 E280A mutation carriers

Authors :
Michael Malek-Ahmadi
Valentina Ghisays
Francisco Lopera
Ronald G. Thomas
Vivek Devadas
Dhruman D. Goradia
Clara Vila-Castelar
Wendy Lee
Joshua T Fox-Fuller
Ji Luo
Natalia Acosta-Baena
Sergio Alvarez
Enmanuelle Pardilla-Delgado
Ana Baena
Alejandro Espinosa
Margarita Giraldo
Silvia Rios-Romenets
Jessica B. Langbaum
Kewei Chen
Edmarie Guzmán-Vélez
Hillary Protas
Yamile Bocanegra
Yinghua Chen
Yi Su
Nan Hu
Yakeel T. Quiroz
Pierre N. Tariot
Eric M. Reiman
David Clayton
Source :
NeuroImage: Clinical, Vol 31, Iss, Pp 102749-(2021), NeuroImage : Clinical
Publication Year :
2021
Publisher :
Elsevier, 2021.

Abstract

Highlights • PET evidence of cerebellar Aβ deposition in unimpaired (CU) PSEN1 E280A kindred. • Cerebellar Aβ PET SUVR began to distinguish CU carriers from non-carriers at age 34. • Cortical and cerebellar Aβ PET SUVR are positively associated in CU carriers. • Cerebellar florbetapir SUVR correlated with lower composite score in CU carriers.<br />Background In contrast to sporadic Alzheimer’s disease, autosomal dominant Alzheimer’s disease (ADAD) is associated with greater neuropathological evidence of cerebellar amyloid plaque (Aβ) deposition. In this study, we used positron emission tomography (PET) measurements of fibrillar Aβ burden to characterize the presence and age at onset of cerebellar Aβ deposition in cognitively unimpaired (CU) Presenilin-1 (PSEN1) E280A mutation carriers from the world’s largest extended family with ADAD. Methods 18F florbetapir and 11C Pittsburgh compound B (PiB) PET data from two independent studies – API ADAD Colombia Trial (NCT01998841) and Colombia-Boston (COLBOS) longitudinal biomarker study were included. The tracers were selected independently by the respective sponsors prior to the start of each study and used exclusively throughout. Template-based cerebellar Aβ-SUVR (standard-uptake value ratios) using a known-to-be-spared pons reference region (cerebellar SUVR_pons), to a) compare 28–56-year-old CU carriers and non-carriers; b) estimate the age at which cerebellar SUVR_pons began to differ significantly in carrier and non-carrier groups; and c) characterize in carriers associations with age, cortical SUVR_pons, delayed recall memory, and API ADAD composite score. Results Florbetapir and PiB cerebellar SUVR_pons were significantly higher in carriers than non-carriers (p

Details

Language :
English
ISSN :
22131582
Volume :
31
Database :
OpenAIRE
Journal :
NeuroImage: Clinical
Accession number :
edsair.doi.dedup.....35a688933278abd635f082797b4a4eb1