Recent advances from metabolomics and lipidomics application in alzheimer’s disease inspiring drug discovery

ABSTRACT

Introduction: Although age is a major risk factor for Alzheimer’s disease (AD), it is not an inevitable consequence of aging nor is it exclusively an old-age disease. Several other major risk factors for AD are strongly associated with metabolism and include lack of exercise, obesity, diabetes, high blood pressure and cholesterol, over-consumption of alcohol and depression in addition to low educational level, social isolation, and cognitive inactivity. Approaches for Alzheimer prevention and treatment through manipulation of metabolism and utilization of active metabolites have great potential either as a primary or secondary treatment avenue or as a preventative strategy in high-risk individuals.

Areas covered: This review outlines the current knowledge concerning the relationship between AD and metabolism and the novel treatments attempting to correct changes in AD patients determined through metabolomics or lipidomic analyses.

Expert opinion: Metabolites are one of the main driving factors and indicators of AD and can offer many possible avenues for prevention and treatment. However, with the highly interconnected effects of metabolites and metabolism, as well as the many different routes for metabolism dysfunction, successful treatment would have to include the correction of metabolic errors as well as errors in transport and metabolite processing in order to affect and revert AD progression.

KEYWORDS:

• Alzheimer’s disease
• metabolism
• metabolomics
• lipidomics

Article highlights

• Alzheimer’s disease (AD) is the most common of the age-related dementias with a projected expectation to become a major challenge in aging populations.

• Both diagnosis and treatment are still lacking for this disease and none of the many clinical trials conducted between 1984 and 2017 (33 years) have provided any improvement in clinical outcomes.

• Metabolites and metabolism have several proposed roles in Alzheimer’s disease development and progression.

• The number of major metabolite groups including amino acids, sugars, vitamins, bile acids, and lipids have a proposed role in Alzheimer’s disease development but individual trials attempting to treat this disease through metabolite treatment have failed thus far.

• With the diversity of possible avenues for Alzheimer disease development, it will be important to explore subtypes of the disease and to try to correct the whole cascade of metabolic errors in order to provide any relief to patients.

• Isolated treatment, only correcting some of the observed insufficiencies cannot lead to disease improvement if viewed in isolation from other steps in the metabolic process.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

A Badhwar is currently supported by a CIHR Postdoctoral Fellowship, the Canadian Consortium on Neurodegeneration in Aging (CCNA), and the Courtois Foundation. M. Cuperlovic-Culf is also supported by the National Research Council of Canada.