MR Elastography Reveals Lower Hippocampal Stiffness in Middle-Aged APOE ε4 Carriers Without Cognitive Impairment

Motivation: Brain tissue softening is well documented in dementia populations. However, preclinical changes to tissue mechanical properties are currently unknown, despite the impact it may have on Alzheimer's disease (AD) development through mechanobiological signalling pathways. Goal(s): To establish whether brain mechanical properties differ in asymptomatic individuals who may be in the preclinical stages of AD. Approach: Apply validated, high-resolution MR elastography methods to cognitively unimpaired, middle-aged APOE-ε4 carriers and APOE-ε3 homozygotes. Results: Lower hippocampal tissue stiffness was observed in APOE-ε4 carriers relative to APOE-ε3 homozygotes, despite the absence of cognitive impairment. There was also a trend to suggest higher thalamus stiffness in APOE-ε4 carriers. Impact: MR elastography is a valuable tool for studying at-risk populations. Future research should determine if preclinical changes in tissue mechanics influence Alzheimer's disease pathogenesis. Findings also have broader implications for precision medicine and risk stratification in dementia research.