NeurOmics Technology: Advancing our Understanding of Neurodegenerative Diseases and Dementia

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Background

The global prevalence of neurodegeneration and dementia will continue to rapidly increase as life expectancy rises. The prevalence of these devastating diseases imposes a major health and socioeconomic burden on patients, robbing them of their independence and further impacting their families and communities. Despite these diseases being distinct clinical entities, neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, vascular dementia, and dementia with Lewy bodies can share cognitive and motor system deficits as well as shared molecular mechanisms of pathogenesis. There has been tremendous progress in the development of genotyping and sequencing technology to resolve the genomic architecture across the neurological spectrum. This presents an exciting genetic-based neurotherapeutic opportunity beginning first with rare inherited neurodegenerative diseases by leveraging CRISPR genome editing among other dosage reduction approaches, and eventually, extending to more common, complex forms of neurodegeneration.

The application of human genomic studies has led to advances in discovering rare causal mutations as well as common risk alleles and understanding their complex relationship with the neurodegenerative phenotype. Early success came from studying highly penetrant mutations in single genes within and across families and revealed the genetic heterogeneity of these diseases, in which multiple genes can give risk to similar neurological phenotypes. Despite the success generated from these studies, these highly penetrant mutations explain a small proportion of neurodegeneration. The post-genomic era ushered in genome-wide association studies and later, next-generation sequencing (massively parallel sequencing), which were successfully leveraged to discover hundreds of common disease loci with individually small effect sizes as well as novel Mendelian genes via rare variant association analyses. Today, with over a decade of massively parallel sequencing experience, we continue to see the development of novel ‘omics’ (genomics, transcriptomics, proteomics) approaches to resolve the molecular basis of neurodegeneration.

In this Research Topic, we seek to learn about the application of emerging –omics technologies and tools to advance our understanding of the defective mechanisms and pathways resulting in neurodegeneration. Furthermore, this collection aims to highlight how and whether personalized treatment has been propelled, based on genomic signatures in neurodegeneration akin to what has been achieved in cancer and cardiovascular disorders. We also seek to learn the current strategies and latest advances in targeted gene delivery or dosage reduction for neurological disorders, and whether this approach can be extended to the treatment of more complex neurological disorders.

Areas of interest include, but are not limited to the following:

• The application of novel –omics (genomics, transcriptomics, proteomics) technology to advance our understanding of the causes, mechanisms, and treatment of dementia and neurodegenerative diseases.
• The identification of novel genes, lead genetic candidates, or pathways yielded from novel technology.
• Genomic profiling and clinical trials in neurodegeneration: are we there yet?
• The utility of polygenic risk scores in neurodegeneration, dementia, and psychiatric conditions.
• The use of clinical and biological biobanks and health records in advancing neurodegeneration science.
• Advances in gene therapy for neurodegenerative disorders and dementia.

We welcome clinical, translational, or basic research in the form of Original Research, Perspectives, Opinions, or Reviews.

Topic Editor, Dr. Michael Nalls, is the founder and consultant of Data Tecnica International, DTI. The other Topic Editors declare no competing interests with regard to the Research Topic subject.

Keywords: Neurodegeneration, Dementia, Genomics, Transcriptomics, Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia

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