Cortical microstructural associations with CSF amyloid and pTau.

Area of Science:

• Neuroimaging
• Neurodegenerative Diseases
• Biomarkers

Background:

• Alzheimer's disease (AD) pathology begins in the cortex, yet early detection remains challenging.
• Diffusion MRI (dMRI) offers non-invasive insights into brain microstructural properties.
• Few studies have explored advanced multi-shell dMRI models like NODDI and MAP-MRI in the cortex for AD.

Purpose of the Study:

• To investigate the relationship between cerebrospinal fluid (CSF) biomarkers (pTau181, Aβ1-42) and cortical dMRI indices (NODDI, MAP-MRI).
• To compare the sensitivity of dMRI measures versus cortical thickness in detecting early AD-related changes.
• To explore the role of dMRI in mediating the link between AD biomarkers and cognitive performance.

Main Methods:

• Analysis of multi-shell dMRI data (NODDI, MAP-MRI) from 66 participants (cognitively unimpaired, mild cognitive impairment, dementia) in the Alzheimer's Disease Neuroimaging Initiative.
• Correlation of regional cortical dMRI indices with CSF levels of pTau181 and Aβ1-42.
• Comparison of dMRI findings with conventional cortical thickness measures and their association with logical memory performance.

Main Results:

• Lower CSF Aβ1-42 and higher pTau181 were associated with increased diffusivity and less restricted diffusion in cortical dMRI measures.
• Cortical dMRI measures showed broader associations with Aβ1-42 than pTau181 and better distinguished Aβ+ from Aβ- individuals compared to pTau status.
• dMRI associations mediated the relationship between CSF biomarkers and impaired logical memory, suggesting sensitivity to early neurodegeneration.

Conclusions:

• Advanced cortical dMRI metrics, particularly those reflecting microstructural integrity, are more sensitive to early Alzheimer's disease pathogenesis than standard cortical thickness.
• dMRI may serve as a valuable tool for elucidating mechanisms of cognitive decline in early AD and for tracking subtle neurodegeneration.
• These findings highlight the potential of dMRI for non-invasive assessment of AD-related microstructural damage.