A longitudinal multimodal in vivo molecular imaging study of the 3xTg-AD mouse model shows progressive early hippocampal and taurine loss

Human Molecular Genetics
Samuel ChiquitaMiguel Castelo-Branco

Abstract

The understanding of the natural history of Alzheimer's disease (AD) and temporal trajectories of in vivo molecular mechanisms requires longitudinal approaches. A behavioral and multimodal imaging study was performed at 4/8/12 and 16 months of age in a triple transgenic mouse model of AD (3xTg-AD). Behavioral assessment included the open field and novel object recognition tests. Molecular characterization evaluated hippocampal levels of amyloid β (Aβ) and hyperphosphorylated tau. Magnetic resonance imaging (MRI) included assessment of hippocampal structural integrity, blood-brain barrier (BBB) permeability and neurospectroscopy to determine levels of the endogenous neuroprotector taurine. Longitudinal brain amyloid accumulation was assessed using 11C Pittsburgh compound B positron emission tomography (PET), and neuroinflammation/microglia activation was investigated using 11C-PK1195. We found altered locomotor activity at months 4/8 and 16 months and recognition memory impairment at all time points. Substantial early reduction of hippocampal volume started at month 4 and progressed over 8/12 and 16 months. Hippocampal taurine levels were significantly decreased in the hippocampus at months 4/8 and 16. No differences were found ...Continue Reading

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Citations

Jun 20, 2020·NMR in Biomedicine·Maria Fatima FalangolaJens H Jensen
Feb 9, 2021·Frontiers in Aging Neuroscience·Joseph A McQuailThomas C Foster
Feb 20, 2021·Molecular Neurobiology·Ana Catarina Rodrigues-NevesAntónio Francisco Ambrósio
Mar 14, 2021·Molecular Neurobiology·Peng-Fei ZhangJin-Tai Yu
Apr 14, 2021·Nature Communications·Ki KimArya Biragyn
Jul 7, 2021·Magnetic Resonance Imaging·Maria Fatima FalangolaJens H Jensen
Jul 25, 2021·International Journal of Molecular Sciences·Chiara MagriMassimo Gennarelli

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Methods Mentioned

BETA
transgenic
imaging techniques
Enzyme-Linked Immunosorbent Assay
ELISA
electrophoresis

Software Mentioned

MRICron
Observador
SPSS
Maze
GraphPad
Quantity One
ANY
SNAP
GraphPad Prism
Matlab

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