Recent Advances in Understanding of Alzheimer's Disease Progression through Mass Spectrometry-Based Metabolomics.

Jericha Mill,Lingjun Li

doi:10.1007/s43657-021-00036-9

Abstract

Alzheimer's disease (AD) is the leading cause of dementia in the aging population, but despite extensive research, there is no consensus on the biological cause of AD. While AD research is dominated by protein/peptide-centric research based on the amyloid hypothesis, a theory that designates dysfunction in beta-amyloid production, accumulation, or disposal as the primary cause of AD, many studies focus on metabolomics as a means of understanding the biological processes behind AD progression. In this review, we discuss mass spectrometry (MS)-based AD metabolomics studies, including sample type and preparation, mass spectrometry specifications, and data analysis, as well as biological insights gleaned from these studies, with the hope of informing future AD metabolomic studies.

Highlights

Alzheimer’s disease (AD) is the most common cause of dementia in the aging population and the sixth-leading cause of death in the United States
The aforementioned sets of criteria are similar in many ways, but their differences are not insignificant; a study comparing DSM-IV plus NINCDS-ADRDA to National Institute of Aging-Alzheimer’s Association (NIA-AA) found that the two means of diagnosis agreed only 70% of the time on the same patient cohort (Dolci et al 2017)
It is unclear which of the metabolic changes in AD are directly contributing to AD pathology and which are compensatory mechanisms to correct dysfunction of another pathway

Summary

Introduction

Alzheimer’s disease (AD) is the most common cause of dementia in the aging population and the sixth-leading cause of death in the United States. As the burden of AD grows larger worldwide, there is an increasing need to diagnose AD early in its progression. AD diagnosis requires the patient to show significant behavioral and cognitive decline; studies have shown that by the time clinical symptoms are showing, cellular decline could already have been occurring for the past 20 years (Wilkins and Trushina 2018). Many early AD biomarker studies used postmortem brain tissue as a source of biomarker molecules, but as brain tissue is not a viable sample source for biomarker screening in living patients, attention has turned to circulating biofluids. We explore the past 5 years of MS-based AD biomarker research to reveal overlap between different biofluids and pathways that warrant additional research. In the interest of focusing on MS technique, NMR spectroscopy is outside the scope of this. But a detailed comparison of the two techniques can be found elsewhere (Emwas 2015)

Study Design

Analysis Methods

Findings

Concluding Remarks and Outlook