Abstract
Neurodegenerative diseases are etiologically and clinically heterogeneous conditions, often reflecting a spectrum of disease rather than well-defined disorders. The underlying molecular complexity of these diseases has made the discovery and validation of useful biomarkers challenging. The search of characteristic genetic and transcriptomic indicators for preclinical disease diagnosis, prognosis, or subtyping is an area of ongoing effort and interest. The next generation of biomarker studies holds promise by implementing meaningful longitudinal and multi-modal approaches in large scale biobank and healthcare system scale datasets. This work will only be possible in an open science framework. This review summarizes the current state of genetic and transcriptomic biomarkers in Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis, providing a comprehensive landscape of recent literature and future directions.
Highlights
In 1998, the National Institutes of Health’s Biomarkers Definitions Working Group defined a biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” [1]
This review aims at providing a general overview on the current status of genetic and transcriptomic biomarkers in the era of big data and precision medicine by focusing on the most common neurodegenerative diseases, including Parkinson’s disease (PD), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS)
The PSEN1 and PSEN2 genes, on chromosomes 14 and 1, respectively, encode presenilins which make up the catalytic subunit of the γ-secretase complex, the complex responsible for the cleavage of amyloid precursor proteins which lead to formation of β-amyloid peptides [42]
Summary
In 1998, the National Institutes of Health’s Biomarkers Definitions Working Group defined a biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” [1]. A plethora of studies have been conducted in an attempt to unravel biomarkers that may be characteristic indicators for preclinical disease diagnosis (before clinical symptoms occur), predictive prognosis, and disease subtyping. In this arena, the search may be difficult because these conditions are not clearly defined entities. Biomarker studies conducted in the field of neurogenetics have usually focused on identifying single biomarker metrics with limited applicability (Table 1). These genetic markers are often disease-causing deleterious mutations responsible for monogenic forms of disease. We assess the progress achieved so far and discuss the main challenges and limitations in our way to dissect the complexity underlying these debilitating conditions
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