Hippocampal Subfields Shine in Early Alzheimer’s Detection

Published on August 12, 2022

Imagine the human brain as a bustling city, with different neighborhoods representing different parts of the brain. Researchers used advanced imaging techniques to explore one particular area, the hippocampus, in individuals without symptoms of Alzheimer’s disease (AD). By examining the morphometry, connectivity, and microstructure of specific subsections within the hippocampus, they discovered that certain regions, like the subiculum and CA1-3, are more vulnerable to early signs of AD pathology. Interestingly, it was found that tau protein levels played a significant role in driving these changes, while amyloid-β levels were less influential. Furthermore, the imaging metrics correlated with neuropsychological assessments, suggesting that these non-invasive techniques could serve as potential predictive biomarkers for AD. Future studies could delve deeper into understanding how these sensitive hippocampal subfields are affected and explore therapeutic interventions that target these areas specifically.

While hippocampal atrophy and its regional susceptibility to Alzheimer’s disease (AD) are well reported at late stages of AD, studies of the asymptomatic stage of AD are limited but could elucidate early stage pathophysiology as well as provide predictive biomarkers. In this study, we performed multi-modal magnetic resonance imaging (MRI) to estimate morphometry, functional connectivity, and tissue microstructure of hippocampal subfields in cognitively normal adults including those with asymptomatic AD. High-resolution resting-state functional, diffusion and structural MRI, cerebral spinal fluid (CSF), and neuropsychological evaluations were performed in healthy young adults (HY: n = 40) and healthy older adults with negative (HO−: n = 47) and positive (HO+ : n = 25) CSF biomarkers of AD. Morphometry, functional connectivity, and tissue microstructure were estimated from the structural, functional, and diffusion MRI images, respectively. Our results indicated that normal aging affected morphometry, connectivity, and microstructure in all hippocampal subfields, while the subiculum and CA1-3 demonstrated the greatest sensitivity to asymptomatic AD pathology. Tau, rather than amyloid-β, was closely associated with imaging-derived synaptic and microstructural measures. Microstructural metrics were significantly associated with neuropsychological assessments. These findings suggest that the subiculum and CA1-3 are the most vulnerable in asymptomatic AD and tau level is driving these early changes.

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