Alz Res Therapy: Patients with dementia have lower blood and urine serotonin

It used to be related to systemic inflammation and the destruction of the serotonergic signaling system
.

In terms of metabolism, a common link between these two biological processes is the breakdown of the essential amino acid tryptophan

It is reported that the metabolites derived from this metabolic pathway are related to the AD disease state and the levels of AD-related proteins, amyloid-β, and neurofilament light chain
.

The secondary metabolic pathways occur in tryptophan hydroxylase and 5-hydroxytryptophan decarboxylase, leading to the production of the key neurotransmitter serotonin

The mechanism of this effect is that serotonin receptor activation up-regulates the activity of α-secretase, which shifts the cleavage of amyloid precursor protein from β- and γ-secretase pathways and reduces the production of amyloid β

During the period of host systemic inflammation, IDO is upregulated by circulating cytokines, thereby increasing the metabolic turnover of tryptophan to kynurenine
.

Therefore, it is reported that the kynurenine/tryptophan ratio is a biomarker for detecting systemic inflammation in diseases

diagnosis

However, such investigations are usually limited to small pilot studies and do not cover all the metabolites involved in these two pathways
.

Related biological pathways involving health and disease can be effectively investigated through a technique called metabolic phenotype
.

This technique is now often used in large epidemiology and clinical cohorts to investigate metabolic changes that affect population health and disease

In this way, Luke Whiley of Imperial College London and others used a multi-stage metabolic phenotyping study to analyze the tryptophan and its metabolites in the urine and serum of control participants diagnosed with AD, MCI and age-matched controls.
The level was investigated
.

The levels of tryptophan and its metabolites in urine and serum of control participants diagnosed with AD, MCI and age-matched were investigated
.

The metabolic phenotype was used in urine (n = 560) and serum (n = 354) in the AddNeuroMed/Dementia Case Register (DCR) biobank in Europe
.

The metabolite data was then asked to understand the differences between the groups; the effects of gender and age; the comparison between the two subgroups of MCI--with those who maintained cognitive stability during follow-up (sMCI); and those who experienced People with further cognitive decline (cMCI); and the effect of selective serotonin reuptake inhibitor (SSRI) drugs on the concentration of metabolites

The results showed that the concentration of tryptophan pathway metabolites in the AD group was significantly lower: 5-hydroxytryptamine (urine, serum), 5-hydroxyindoleacetic acid (urine), kynurenine (serum), kynurenic acid (urine), Tryptophan (urine, serum), xanthine (urine, serum), and kynurenic acid/tryptophan ratio (urine)
.

For each of the listed metabolites, the observed decrease in concentration is consistent with the clinical diagnosis: control>MCI>AD
.

There was no significant difference between the two MCI subgroups, and the SSRI drug treatment status affected the observation in serum but not urine

The important significance of this study lies in the discovery: Compared with the control group, the urine and serum serotonin concentrations of AD patients are significantly lower, which indicates that the bioavailability of neurotransmitters may change in the disease
.

Compared with the control group, the urine and serum serotonin concentrations of AD patients were significantly lower, indicating that the bioavailability of neurotransmitters may change in the disease
.

Original source: on behalf of AddNeuroMed consortium, Whiley L, Chappell KE, et al.

Metabolic phenotyping reveals a reduction in the bioavailability of serotonin and kynurenine pathway metabolites in both the urine and serum of individuals living with Alzheimer's disease.
Alz Res Therapy.
2021 ;13(1):20.
doi:10.
1186/s13195-020-00741-z

Metabolic phenotyping reveals a reduction in the bioavailability of serotonin and kynurenine pathway metabolites in both the urine and serum of individuals living with Alzheimer's disease.

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