Histological validation of Quantitative Gradient Recalled Echo (qGRE) MRI as in vivo early neurodegeneration biomarker in Alzheimer’s Disease

Motivation: Robust methods are urgently needed for preclinical evaluation of novel Alzheimer Disease (AD) therapies to accelerate drug discovery. MRI methods hold significant promise, with quantitative Gradient Recalled Echo (qGRE) shown to provide insight into neurodegeneration in AD prior to atrophy development in humans. Goal(s): In this study a novel method is shown to non-invasively measure the longitudinal neuronal loss in the hippocampus of a mouse model of AD. Approach: Histological validation of the findings is performed. Results: A strong correlation is revealed between the MRI metric and myelin content, hence offering the explanation for the mechanism of observed contrast. Impact: A robust method for longitudinal in-vivo quantification of neuronal density loss in a mouse model of AD is presented and validated, allowing for efficient preclinical evaluation of novel AD therapeutics and accelerated drug development in the field.