👤 Florge Francis Arnejo Sy

Neurodegenerative diseases, marked by complex molecular mechanisms and diverse clinical features, challenge conventional research approaches. This chapter emphasizes the value of multi-omics integration in understanding the biology of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). Genomic studies reveal risk variants such as APOE ε4 in Alzheimer's and rare mutations in familial forms. Transcriptomics highlights gene expression changes, including synaptic dysfunction in early Parkinson's and alternative splicing errors in TARDBP-related ALS. Proteomics identifies key protein aggregates like amyloid beta and alpha-synuclein, along with modifications such as hyperphosphorylated tau that correlate with cognitive decline. Metabolomics uncovers metabolic alterations, including mitochondrial dysfunction in Parkinson's and lipid peroxidation in ALS, which contribute to disease progression. By combining these layers with high-throughput tools like single-cell sequencing, spatial transcriptomics, and mass spectrometry, researchers can reconstruct molecular networks linking genetic risk, gene regulation, protein dysfunction, and metabolic imbalance. This approach enables patient stratification into molecular subtypes, such as neuroinflammatory clusters defined by microglial gene signatures and cytokine expression. Biomarkers from blood and cerebrospinal fluid allow for minimally invasive disease monitoring. Despite challenges such as data heterogeneity and limited standardization, multi-omics approaches support biomarker discovery and therapeutic development. Integrating these datasets with neuroimaging and digital tools enhances diagnostic precision and guides targeted interventions, such as antisense therapies for SOD1-linked ALS. Multi-omics integration is thus a critical foundation for advancing personalized strategies in neurodegenerative disease research. Show less

In forensics, one-third of sudden deaths remain unexplained after a forensic autopsy. A majority of these sudden unexplained deaths (SUDs) are considered to be caused by inherited cardiovascular diseases. In this study, we investigated 40 young SUD cases (<40 years), with non-diagnostic structural cardiac abnormalities, using Targeted NGS (next-generation sequencing) for 167 genes previously associated with inherited cardiomyopathies and channelopathies. Fifteen cases identified 17 variants on related genes including the following: Show less

Genetic heart disease is a common cause of sudden cardiac arrest (SCA) in the young and those without an ischaemic precipitant. Identifying a cause of SCA in these patients allows for targeted care and family screening. Current guidelines recommend limited, phenotype-guided genetic testing in SCA survivors where a specific genetic condition is suspected and genetic testing is not recommended in clinically-idiopathic SCA survivors. To investigate the diagnostic utility of broad, multi-phenotype genetic testing in clinically-idiopathic SCA survivors. Clinically-idiopathic SCA survivors underwent analysis of genes known to be associated with either cardiomyopathy or primary arrhythmia syndromes, following referral to a specialised genetic heart disease clinic in Sydney, Australia between 1997 and 2019. Comprehensive review of clinical records, investigations and re-appraisal of genetic data according to current variant classification criteria was performed. In total, 22% (n = 8/36) of clinically-idiopathic SCA survivors (mean age 36.9 ± 16.9 years, 61% male) had a disease-causing variant identified on broad genetic testing. Of these, 7 (88%) variants resided in cardiomyopathy-associated genes (ACTN2, DES, DSP, MYBPC3, MYH7, PKP2) despite structurally normal hearts or sub-diagnostic structural changes at the time of arrest, so-called "concealed cardiomyopathy". Only one SCA survivor had a variant identified in a channelopathy associated gene (SCN5A). Extended molecular analysis with multi-phenotype genetic testing can identify a "concealed cardiomyopathy", and increase the diagnosis rate for clinically-idiopathic SCA survivors. Show less

Recent genome-wide association studies have shown associations between multiple genetic variants and primary restless legs syndrome (RLS). Their roles in end stage renal disease (ESRD) related secondary RLS are not clear and studies in Asian populations are scarce. The association between candidate genetic variants and uremic RLS was investigated in a large cohort of Taiwanese dialysis patients. Sixteen RLS-related genetic variants at six loci, including MEIS1, BTBD9, MAP2K5/SKOR1, PTPRD, TOX3/BC034767 and the intergenic region of chromosome 2p14, in a total of 993 ESRD patients (259 subjects with and 734 subjects without RLS) were genotyped using TaqMan genotyping assays. Multivariate logistic regression analysis was used to test for associations between the genotypes and RLS in ESRD. Power calculations were completed using the CATs Genetic Power Calculator with settings of a multiplicative genetic model. A modest association between the PTPRD variant rs4626664 and uremic RLS (odds ratio 1.52, 95% CI 1.03-2.23, P = 0.03) and a trend that TOX3/BC034767 variant rs3104767 may associate with the occurrence of RLS were observed in our dialysis population (odds ratio 1.74, 95% CI 0.97-3.11, P = 0.06). No associations between other genetic variants and risk and severity of RLS were observed in our ESRD cohort. The genetic variants of primary RLS candidate genes did not play a major role in our uremic RLS populations. The ethnic difference and heterogeneous etiologies underlying renal failure may partly explain the minor genetic contribution to uremic RLS in our populations. Further studies for other ethnicities will be of worth. Show less