Morphometric similarity differences in drug‐naive Parkinson's disease correlate with transcriptomic signatures

Abstract

BackgroundDifferences in cortical morphology have been reported in individuals with Parkinson's disease (PD). However, the pathophysiological mechanism of transcriptomic vulnerability in local brain regions remains unclear.ObjectiveThis study aimed to characterize the morphometric changes of brain regions in early drug‐naive PD patients and uncover the brain‐wide gene expression correlates.MethodsThe morphometric similarity (MS) network analysis was used to quantify the interregional structural similarity from multiple magnetic resonance imaging anatomical indices measured in each brain region of 170 early drug‐naive PD patients and 123 controls. Then, we applied partial least squares regression to determine the relationship between regional changes in MS and spatial transcriptional signatures from the Allen Human Brain Atlas dataset, and identified the specific genes related to MS differences in PD. We further investigated the biological processes by which the PD‐related genes were enriched and the cellular characterization of these genes.ResultsOur results showed that MS was mainly decreased in cingulate, frontal, and temporal cortical areas and increased in parietal and occipital cortical areas in early drug‐naive PD patients. In addition, genes whose expression patterns were associated with regional MS changes in PD were involved in astrocytes, excitatory, and inhibitory neurons and were functionally enriched in neuron‐specific biological processes related to trans‐synaptic signaling and nervous system development.ConclusionsThese findings advance our understanding of the microscale genetic and cellular mechanisms driving macroscale morphological abnormalities in early drug‐naive PD patients and provide potential targets for future therapeutic trials.

Transcriptional expression patterns of the cortical morphometric similarity network in progressive supranuclear palsy

“… 21 In addition, MSN may be perceived as a neuroimaging characteristic that connects alterations in brain structure to transcriptional information. 22 , 23 Recent studies have shown that clinical abnormalities of the MSN in diseases such as Parkinson's disease, 24 schizophrenia, 25 and major depressive disorder 22 are strongly correlated with the brain expression of disease‐related genes, revealing the transcriptome and cell pattern vulnerability of the regional brain to neurogenetic diseases. 23 Although the use of MSN is a reliable and powerful method, morphological differences in PSP have not been investigated.…”