Novel insights into early Alzheimer's disease: quantitative gradient recalled echo MRI reveals preatrophic neuronal and myelin injury concurrent with emerging amyloid pathology

BACKGROUND Brain amyloid accumulation is considered an early sign of Alzheimer's disease (AD) pathology, appearing decades before manifestation of clinical symptoms. However, very little is known about neurodegeneration during this early AD stage. Herein we use quantitative gradient recalled echo (qGRE) magnetic resonance imaging (MRI) to reveal preatrophic microstructural neuronal and myelin damage concurrent with amyloid pathology. METHODS qGRE MRI and positron emission tomography (PET) amyloid [ 11 C] Pittsburgh Compound‐B ( 11 C‐PiB) images were acquired concurrently from 141 study participants. Two qGRE‐derived biomarker indices – neuronal density index (NDI) (a proxy for neuronal density) and myeline density index (MDI) (a proxy for myelin density) – are used here to quantify neuronal and myelin damage. RESULTS qGRE detected significantly lower gray matter neuronal density and white matter myelination in the group of participants with amyloid level below the conventional amyloid‐positive threshold (mean cortical standardized uptake value ratio of 1.42), despite the absence of atrophy. DISCUSSION qGRE‐based NDI and MDI in‐vivo biomarkers identify microstructural brain preatrophic neurodegeneration and demyelination in early amyloid pathology.