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PET evidence of preclinical cerebellar amyloid plaque deposition in autosomal dominant Alzheimer’s disease-causing Presenilin-1 E280A mutation carriers
- 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
- Subjects :
- Adult
Cerebellum
Pathology
medicine.medical_specialty
Amyloid
Cognitive Neuroscience
Computer applications to medicine. Medical informatics
R858-859.7
Plaque, Amyloid
Brain imaging
Presenilin
chemistry.chemical_compound
Neuroimaging
Alzheimer Disease
Pons
Presenilin-1
medicine
PSEN1
Humans
Radiology, Nuclear Medicine and imaging
RC346-429
Amyloid beta-Peptides
Aniline Compounds
medicine.diagnostic_test
business.industry
Regular Article
Middle Aged
Cross-Sectional Studies
medicine.anatomical_structure
PET
Autosomal dominant Alzheimer’s disease
nervous system
Neurology
chemistry
Positron emission tomography
Positron-Emission Tomography
Mutation
Neurology (clinical)
Neurology. Diseases of the nervous system
Pittsburgh compound B
business
Subjects
Details
- Language :
- English
- ISSN :
- 22131582
- Volume :
- 31
- Database :
- OpenAIRE
- Journal :
- NeuroImage: Clinical
- Accession number :
- edsair.doi.dedup.....35a688933278abd635f082797b4a4eb1