Multimodal Imaging in Rat Model Recapitulates Alzheimer's Disease Biomarkers Abnormalities

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Maxime J ParentP Rosa-Neto

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 pro...Continue Reading

Citations

Nov 14, 2018·American Journal of Physiology. Endocrinology and Metabolism·Joshua A KulasColin K Combs
Aug 24, 2019·Frontiers in Aging Neuroscience·Raúl TudelaGuadalupe Soria
Jun 28, 2020·Molecular Psychiatry·Min Su KangUNKNOWN Alzheimer’s Disease Neuroimaging Initiative
May 18, 2019·Current Alzheimer Research·Leonardo Guzman-MartinezLeonardo P Navarrete
Jan 8, 2020·Biomolecules·Haroon KhanEsra Küpeli Akkol
Mar 20, 2019·Frontiers in Pharmacology·A Claudio CuelloSonia Do Carmo
Jul 5, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·J C RyuS O Yoon
Mar 11, 2020·Frontiers in Aging Neuroscience·Marcelo FeboThomas C Foster
May 23, 2018·Disease Models & Mechanisms·Mazen Asaad, Jin Hyung Lee
Feb 9, 2021·Frontiers in Aging Neuroscience·Joseph A McQuailThomas C Foster
Aug 12, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Min Su KangPedro Rosa-Neto

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Methods Mentioned

BETA
transgenic
ELISA

Software Mentioned

Axiovision
MINC
ANY
maze

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