1. Multimodal Imaging in Rat Model Recapitulates Alzheimer's Disease Biomarkers Abnormalities.
- Author
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Parent, Maxime J., Zimmer, Eduardo R., Shin, Monica, Min Su Kang, Fonov, Vladimir S., Mathieu, Axel, Aliaga, Antonio, Kostikov, Alexey, Do Carmo, Sonia, Dea, Doris, Poirier, Judes, Soucy, Jean-Paul, Gauthier, Serge, Cuello, A. Claudio, and Rosa-Neto, Pedro
- Subjects
BRAIN imaging ,AMYLOIDOSIS diagnosis ,ALZHEIMER'S disease ,AMYLOID beta-protein ,LABORATORY rats - Abstract
Imaging biomarkers are frequently proposed as endpoints for clinical trials targeting brain amyloidosis in Alzheimer's disease (AD); however, the specific impact of amyloid-β (Aβ) aggregation on biomarker abnormalities remains elusive in AD. Using the McGill-R-Thyl- APP transgenic rat as a model of selective Aβ pathology, we characterized the longitudinal progression of abnormalities in biomarkers commonly used in AD research. Middle-aged (9-11 months) transgenic animals (both male and female) displayed mild spatial memory impairments and disrupted cingulate network connectivity measured by resting-state fMRI, even in the absence of hypometabolism (measured with PET (
18 F]FDG) or detectable fibrillary amyloidosis (measured with PET [18 F]NAV4694). At more advanced ages (16-19 months), cognitive deficits progressed in conjunction with resting connectivity abnormalities; furthermore, hypometabolism, Aβ plaque accumulation, reduction of CSF Aβ1-42 concentrations, and hippocampal atrophy (structural MRI) were detectable at this stage. The present results emphasize the early impact of Aβ on brain connectivity and support a framework in which persistent Aβ aggregation itself is sufficient to impose memory circuits dysfunction, which propagates to adjacent brain networks at later stages. [ABSTRACT FROM AUTHOR]- Published
- 2017
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