Bridging the Gap Between Morphometric Similarity Mapping and Gene Transcription in Alzheimer's Disease.

Yang Zhang,Nan Zhang,Min Ma,Heng Wu,Junlin Shen,Zhonghua Xie

doi:10.3389/fnins.2021.731292

Abstract

Disruptions in brain connectivity have been widely reported in Alzheimer’s disease (AD). Morphometric similarity (MS) mapping provides a new way of estimating structural connectivity by interregional correlation of T1WI- and DTI-derived parameters within individual brains. Here, we aimed to identify AD-related MS changing patterns and genes related to the changes and further explored the molecular and cellular mechanism underlying MS changes in AD. Both 3D-T1WI and DTI data of 106 AD patients and 106 well-matched healthy elderly individuals from the ADNI database were included in our study. Cortical regions with significantly decreased MS were found in the temporal and parietal cortex, increased MS was found in the frontal cortex and variant changes were found in the occipital cortex in AD patients. Mean MS in regions with significantly changed MS was positively or negatively associated with memory function. Negative MS-related genes were significantly downregulated in AD, specifically enriched in neurons, and participated in biological processes, with the most significant term being synaptic transmission. This study revealed AD-related cortical MS changes associated with memory function. Linking gene expression to cortical MS changes may provide a possible molecular and cellular substrate for MS abnormality and cognitive decline in AD.

Highlights

Alzheimer’s disease (AD) is a neurodegenerative disease marked by progressive neuron loss, manifested by short-term memory and other cognitive impairment symptoms (Wang et al, 2020)
Compared with traditional measurements based on a single MRI sequence, Morphometric similarity (MS) considering multiple MRI morphometric indices could reflect the anatomical connections of different brain areas based on histological similarity and axonal connectivity within an individual human brain
This study showed that AD patients had decreased regional MS in multiple AD-susceptible regions in the temporal and parietal cortex

Summary

Introduction

Alzheimer’s disease (AD) is a neurodegenerative disease marked by progressive neuron loss, manifested by short-term memory and other cognitive impairment symptoms (Wang et al, 2020). AD-related neurodegeneration involves several brain regions, in which the entorhinal, hippocampal and temporal cortices are the most reported (Lerch et al, 2005; Im et al, 2008; Morra et al, 2008; Seong et al, 2010; Li et al, 2014; Femminella et al, 2018) Structural indicators of these regions, including gray matter density (Frisoni et al, 2002), volume (Busatto et al, 2003), cortical thickness (Pettigrew et al, 2017), and curvature (Im et al, 2008; Seong et al, 2010), have been found to be decreased in AD patients. MR topological studies constructed whole-brain structural networks and demonstrated abnormal topological properties in multiple brain regions, including the hippocampal, frontal, temporal, parietal and occipital regions, verifying brain network disruption and disconnection between anatomically connected brain regions in AD patients (Lo et al, 2010; Yao et al, 2010)

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