Correlation Between Brain Structure Atrophy and Plasma Amyloid-β and Phosphorylated Tau in Patients With Alzheimer’s Disease and Amnestic Mild Cognitive Impairment Explored by Surface-Based Morphometry
Authors: Li Kaidi , Qu Hang , Ma Mingyi , Xia Chenyu , Cai Ming , Han Fang , Zhang Qing , Gu Xinyi , Ma Qiang 
Published: April 2022

Objective

To investigate the changes in the cortical thickness of the region of interest (ROI) and plasma Aβ40, Aβ42, and phosphorylated Tau (P-Tau) concentrations in patients with Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI) as the disease progressed with surface-based morphometry (SBM), to analyze the correlation between ROI cortical thickness and measured plasma indexes and neuropsychological scales, and to explore the clinical value of ROI cortical thickness combined with plasma Aβ40, Aβ42, and P-Tau in the early recognition and diagnosis of AD.

Methods

This study enrolled 33 patients with AD, 48 patients with aMCI, and 33 healthy controls (normal control, NC). Concentration changes in plasma Aβ42, Aβ40, and P-Tau collected in each group were analyzed. Meanwhile, the whole brain T1 structure images (T1WI-3D-MPRAGE) of each group of patients were collected, and T1 image in AD-aMCI, AD-NC, and aMCI-NC group were analyzed and processed by SBM technology to obtain brain regions with statistical differences as clusters, and the cortical thickness of each cluster was extracted. Multivariate ordered logistic regression analysis was used to screen out the measured plasma indexes and the indexes with independent risk factors in the cortical thickness of each cluster. Three comparative receiver operating characteristic (ROC) curves of AD-aMCI, AD-NC, and aMCI-NC groups were plotted, respectively, to explore the diagnostic value of multi-factor combined prediction for cognitive impairment. The relationship between cortical thickness and plasma indexes, and between cortical thickness and Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores were clarified by Pearson correlation analysis.

Results

Plasma Aβ40, Aβ42, and P-Tau proteins in the NC, aMCI, and AD groups increased with the progression of AD (P &lt; 0.01); cortical thickness reductions in the AD-aMCI groups and AD-NC groups mainly involved the bilateral superior temporal gyrus, transverse temporal gyrus, superior marginal gyrus, insula, right entorhinal cortex, right fusiform gyrus, and cingulate gyrus. However, there were no statistical significances in cortical thickness reductions in the aMCI and NC groups. The cortical thickness of the ROI was negatively correlated with plasma Aβ40, Aβ42, and P-Tau concentrations (P &lt; 0.05), and the cortical thickness of the ROI was positively correlated with MMSE and MoCA scores. Independent risk factors such as Aβ40, Aβ42, P-Tau, and AD-NC cluster 1R (right superior temporal gyrus, temporal pole, entorhinal cortex, transverse temporal gyrus, fusiform gyrus, superior marginal gyrus, middle temporal gyrus, and inferior temporal gyrus) were combined to plot ROC curves. The diagnostic efficiency of plasma indexes was higher than that of cortical thickness indexes, the diagnostic efficiency of ROC curves after the combination of cortical thickness and plasma indexes was higher than that of cortical thickness or plasma indexes alone.

Conclusion

Plasma Aβ40, Aβ42, and P-Tau may be potential biomarkers for early prediction of AD. As the disease progressed, AD patients developed cortical atrophy characterized by atrophy of the medial temporal lobe. The combined prediction of these region and plasma Aβ40, Aβ42, and P-Tau had a higher diagnostic value than single-factor prediction for cognitive decline.