Gene Expression Profiling as a Novel Diagnostic Tool for Neurodegenerative Disorders

Abstract

There is a lack of effective diagnostic biomarkers for neurodegenerative disorders (NDDs). Here, we established gene expression profiles for diagnosing Alzheimer’s disease (AD), Parkinson’s disease (PD), and vascular (VaD)/mixed dementia. Patients with AD had decreased APOE, PSEN1, and ABCA7 mRNA expression. Subjects with VaD/mixed dementia had 98% higher PICALM mRNA levels, but 75% lower ABCA7 mRNA expression than healthy individuals. Patients with PD and PD-related disorders showed increased SNCA mRNA levels. There were no differences in mRNA expression for OPRK1, NTRK2, and LRRK2 between healthy subjects and NDD patients. APOE mRNA expression had high diagnostic accuracy for AD, and moderate accuracy for PD and VaD/mixed dementia. PSEN1 mRNA expression showed promising accuracy for AD. PICALM mRNA expression was less accurate as a biomarker for AD. ABCA7 and SNCA mRNA expression showed high-to-excellent diagnostic accuracy for AD and PD, and moderate-to-high accuracy for VaD/mixed dementia. The APOE E4 allele reduced APOE expression in patients with different APOE genotypes. There was no association between PSEN1, PICALM, ABCA7, and SNCA gene polymorphisms and expression. Our study suggests that gene expression analysis has diagnostic value for NDDs and provides a liquid biopsy alternative to current diagnostic methods.

Influence of Metabolic, Transporter, and Pathogenic Genes on Pharmacogenetics and DNA Methylation in Neurological Disorders

“…While APOE4 is not a risk factor for PD, it increases the risk of developing dementia and cognitive decline [ 77 ]. The APOE genotype also affects the age of onset and severity of stroke, and individuals with the APOE4 allele exhibit delayed recovery of verbal memory function [ 80 ] and an increased risk of developing stroke-associated dementia [ 81 ]. We and others have shown that APOE expression decreases in venous blood and plasma samples in AD patients, suggesting its potential as a diagnostic biomarker for the disease [ 81 , 82 ].…”

“…The APOE genotype also affects the age of onset and severity of stroke, and individuals with the APOE4 allele exhibit delayed recovery of verbal memory function [ 80 ] and an increased risk of developing stroke-associated dementia [ 81 ]. We and others have shown that APOE expression decreases in venous blood and plasma samples in AD patients, suggesting its potential as a diagnostic biomarker for the disease [ 81 , 82 ]. The expression of APOE mRNA is lower in E4 carriers than in individuals with APOE 2.3 and - 3.3 genotypes [ 29 ].…”

“…The present study proposes that analyzing genotypes related to metabolism, transporters, and pathological pharmacogenetics can be used to analyze the evolution of global DNA methylation levels ( Table 1 ). Other studies have highlighted the correlation between neurodegenerative diseases and decreased levels of sirtuin activity, neurodegenerative gene expression, and global DNA methylation [ 25 , 26 , 81 ]. Furthermore, DNA methylation holds potential as a biomarker for assessing disease progression in patients with neurological disorders [ 29 ].…”

The ABC's of Alzheimer risk gene ABCA7

“…Often studies present contradicting results. While one meta-analysis did not find 96 changes in expression in the frontal lobe, temporal, cerebellum, or parietal lobe (Table 3), 94 another reported higher expression in AD patients across the brain. 95 Two studies investigated expression differences in blood, again with contrasting results, with one reporting higher expression in blood in patients 92 and another a reduction 96 (Table 3).…”

“…While one meta‐analysis did not find changes in expression in the frontal lobe, temporal, cerebellum, or parietal lobe (Table 3 ), 94 another reported higher expression in AD patients across the brain. 95 Two studies investigated expression differences in blood, again with contrasting results, with one reporting higher expression in blood in patients 92 and another a reduction 96 (Table 3 ). Finally, one study investigated ABCA7 protein expression in hippocampus and parietal cortex in individuals with different levels of Braak pathology.…”