Cortical microstructural associations with CSF amyloid and tau. (December 2021) - Nir, Talia M.
Abstract: Background: Multi‐shell diffusion MRI (dMRI) biophysical models can estimate intracellular (ICVF), extracellular (ECVF) and free water (ISOVF) volume fractions (VFs) in brain tissue, and may offer insight into Alzheimer's disease pathological processes. These microstructural measures can be calculated in the cortex using a gray matter specific model that may be sensitive to amyloid and tau burden. Here, we evaluated relationships between regional cortical microstructural VFs and CSF amyloid and tau biomarkers. Method: Multi‐shell dMRI and CSF biomarker data were available for 50 ADNI‐3 participants (age: 72.4±6.4 yrs; 20 male; 36 cognitively normal, 12 MCI, 2 dementia). Cortical ICVF, ECVF and ISOVF were estimated with the multi‐tissue spherical mean technique (MT‐SMT). Mean cortical measures were extracted from 4 lobes and the cingulate cortex, parcellated with FreeSurfer. Random‐effects linear regressions tested associations between regional dMRI measures and CSF pTau or Aβ42/Aβ40 burden, adjusting for age, sex, education, and grouping by scanning site. FDR ( q =0.05) was used to correct for multiple comparisons across 5 regions, 3 diffusion measures, and 2 tests. Result: Higher Aβ42/Aβ40 was associated with lower ISOVF throughout the cortex (Figure 1), and higher ECVF and ICVF in the cingulate, frontal and temporal lobes. Higher ICVF was also found in the parietal cortex. Higher pTau was associated with higher ISOVF in the occipital and parietal lobes, and lower ECVF in the frontal and parietal lobes (Figure 2). No pTau ICVF associations were detected. Conclusion: Lower ICVF and higher ISOVF with greater amyloid and tau may indicate neuronal loss or edema, while lower ECVF could reflect, for example, as neuronal swelling or an influx of activated microglia. Lower ECVF with greater amyloid and tau burden may also reflect accumulation of large hydrophobic amyloid plaques and neurofibrillary tangles in the extracellular space. These results are preliminary and, as many factors influence dMRI measures, should be interpreted with caution. Future work will incorporate multimodal imaging to map associations of diffusion measures with localized PET‐derived amyloid and tau measures.