Blood-based transcriptomic biomarkers are predictive of neurodegeneration rather than Alzheimer’s disease

Abstract

AbstractAlzheimer’s disease (AD) is a growing global health crisis, affecting millions and incurring substantial economic costs. However, clinical diagnosis remains challenging, with misdiagnoses and underdiagnoses prevalent. There is an increased focus on putative, blood-based biomarkers that may be useful for the diagnosis, as well as early detection, of AD. In the present study, we used an unbiased combination of machine learning and functional network analyses to identify blood gene biomarker candidates in AD. Using supervised machine learning, we also determine whether these candidates were indeed unique to AD or whether they were indicative of other neurodegenerative diseases Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). Our analyses showed that genes involved in spliceosome assembly, RNA binding, transcription, protein synthesis, mitoribosomes, and NADH dehydrogenase were the best performing genes for identifying AD patients relative to cognitively healthy controls. This transcriptomic signature, however, was not unique to AD and subsequent machine learning showed that this signature could also predict PD and ALS relative to controls without neurodegenerative disease. Combined, our results suggest that mRNA from whole blood can indeed be used to screen for patients with neurodegeneration but may be less effective at diagnosing the specific neurodegenerative disease.