Multiplexing Biomarker Methods, Proteomics and Considerations for Alzheimer’s Disease

Abstract

Biomarker research for Alzheimer's disease (AD) has been growing rapidly over recent years especially as the number of persons affected by this disease is nearing approximately 46 million worldwide. Single biomarker assays are challenging to establish since AD is multifactorial and complex. In addition to the classic signs of diminished cognition and memory, AD patients can also exhibit symptoms which may be confused with some psychiatric disorders, such as depression. No molecular biomarkers have been established or translated into clinical tools although recent efforts have resulted in addition of molecular biomarker profiles to the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria for research purposes. The three accepted molecular biomarkers are amyloid-βeta peptide 1-42, total tau protein and hyperphosphorylated tau at threonine 181 in human cerebrospinal fluid (CSF). Aside from these three CSF markers, a number of potential candidates have been identified in CSF and other body fluids. In order to identify biomarkers for diagnosis, early prevention, prognosis and response to therapeutic treatment, multiplex biomarker tests will be required. These include multiplex immunoassay and mass spectrometry-based proteomics platforms. Proteomics analyses of bodily fluids such as plasma are growing in number and providing potential targets for further investigation and validation in AD research. This chapter highlights proteomic biomarker assays and their applications and potential use for clinical diagnosis and prognosis of AD.

Alcohol Drinking Exacerbates Neural and Behavioral Pathology in the 3xTg-AD Mouse Model of Alzheimer’s Disease

“…Predictably, many of the alcohol-sensitive proteins are abnormally expressed in the brains of AD patients. Indeed, proteomic studies of CSF/plasma from human Alzheimer's patients (Robinson et al, 2017) and transgenic mouse models of AD (Chang et al, 2013;Fu et al, 2015;Takano et al, 2013) show considerable overlap between AD-linked protein networks and the alcohol-sensitive networks shown here. Notably, heat shock proteins and creatinine kinases were upregulated and total levels of DPYSL2 (CRMP2) a microtubule protein, was decreased in the proteomics study but is consistently hyperphosphorylated in postmortem human brains and transgenic lines.…”

Precision Medicine: Role of Biomarkers in Early Prediction and Diagnosis of Alzheimer’s Disease

“…MS-based proteomics technology is well suited for the biomarker discovery for diseases such as AD [63][64][65]. During the last 10 years, apart from the gel-based techniques (e.g., 2D-PAGE and 2D-DIGE), gel-free techniques (e.g., stable isotope labeling or using label-free methods) have been dominating the field of MS-based quantitation in proteomics [66].…”

Mass spectrometry is a multifaceted weapon to be used in the battle against Alzheimer's disease: Amyloid beta peptides and beyond

“…Therefore, the search for new and reliable possible biomarkers in AD is still an open and widely investigated field. 9 Generally, a biomarker can be a molecule of any sort (protein, lipid, metabolite, metal ion, etc.) as long as it can be accurately measured and evaluated, to indicate normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention.…”

“…Although the former two need the administration of a radioactive imaging agents into a patient, the latter, despite being noninvasive, is quite expensive and cannot detect early stages of the disease when development starts long before any noticeable decrease in hippocampal volume or deposition of plaques and tau tangles). Therefore, the search for new and reliable possible biomarkers in AD is still an open and widely investigated field . Generally, a biomarker can be a molecule of any sort (protein, lipid, metabolite, metal ion, etc.)…”