Annals of neurology: the relationship between the human blood metabolome and Alzheimer's disease risk

Alzheimer's disease (AD) is a progressive neurodegenerative disease that affects approximately 55 million people worldwide

Figure 1: Paper cover image

In addition, recent clinical trials to research and develop AD drugs have also failed

The human metabolome consists of endogenous and exogenous molecules and represents an individual's metabolic fingerprint

With the unprecedented development of mass spectrometry and high-throughput genotyping techniques in recent years, several genome-wide association studies (GWASs) have made great achievements in uncovering the genetic determinants of the human comprehensive metabolome

MR is an emerging method that uses genetic variation as a proxy for the exposure of interest to estimate causal relationships between exposure and disease without the bias of confounding or reverse causality

To fill this gap, Lulu Sun et al.

They selected 119 unique blood metabolites from 3 metabolome genome-wide association studies (GWASs) with 147,827 European participants

MR analysis was performed to assess the association of blood metabolites with AD, and pan-phenotype MR analysis was further applied to identify potential target side effects of metabolite intervention

Four metabolites were identified as causal mediators of AD, including epiandrosterone sulfate (odds increase per SD [OR].

MR analysis revealed that epiandrosterone sulfate, 5α-androstane-3β-17β-diol disulfate, and sphingomyelin mediate the risk of multiple diseases, and glutamine had a beneficial effect on the risk of 4 diseases

The significance of this study lies in the discovery that genetically predicted increases in epiandrosterone sulfate, 5α-androstane-3beta-17beta-diol disulfate and glutamine may be associated with a reduced risk of AD, while sphingolipids Phospholipids were associated with increased risk

Sun L, Guo D, Jia Y, et al.