Multimodal imaging in rat model recapitulates Alzheimer’s disease biomarkers abnormalities

35Citations
Citations of this article
108Readers
Mendeley users who have this article in their library.

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-Thy1-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 [18F]FDG) or detectable fibrillary amyloidosis (measured with PET [18F]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.

Cite

CITATION STYLE

APA

Parent, M. J., Zimmer, E. R., Shin, M., Kang, M. S., Fonov, V. S., Mathieu, A., … Rosa-Neto, P. (2017). Multimodal imaging in rat model recapitulates Alzheimer’s disease biomarkers abnormalities. Journal of Neuroscience, 37(50), 12263–12271. https://doi.org/10.1523/JNEUROSCI.1346-17.2017

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free