Decreased plasmatic spermidine and increased spermine in mild cognitive impairment and Alzheimer’s disease patients

Abstract

Background: Current evidence suggests that upregulation of polyamines system plays a role both in cognitive deficit and synaptic loss observed in Alzheimer's disease (AD). Objective: The aim of this study was to determine the plasmatic concentration of polyamines in mild cognitive impairment (MCI) and AD patients in comparison with healthy controls (HC). Methods: Plasmatic polyamines were quantified using the AbsoluteIDQ® p180 and liquid chromatography coupled to tandem mass spectrometry (LC/MS-MS). Results: The study group comprised 34 AD patients, 20 MCI and 25 HC. All individuals were followed for 4 years. During this period 8 amnestic MCI patients (40% of the MCI sample at baseline) converted to AD. Spermidine level was lower in both patient groups (AD; MCI) compared to HC (p = 0.007). Plasma levels of spermine were higher in the MCI group (p < 0.001), but decreased in the sub-sample of MCI patients who converted to AD (p = 0.043). No statistically significant differences were found in ornithine and putrescine levels (p = 0.056 and p = 0.126, respectively). Discussion: Our results suggest dynamic changes in the expression of polyamines in the MCI-AD continuum.

Molecular Probes, Chemosensors, and Nanosensors for Optical Detection of Biorelevant Molecules and Ions in Aqueous Media and Biofluids

“…359−361 For example, spermidine levels in plasma were lower in both groups of MCIs and AD patients compared to the healthy group, and the concentration of spermine was increased in the MCI group but decreased in the subgroups of MCIs patients who transitioned to AD. 361 In addition, high polyamine levels are usually found in cancer cells, 347,362,363 and their urinary and plasma concentrations may be useful markers of cancer. 364−368 For example, urinary diacetylspermine has been identified as a biomarker for lung and ovarian cancer.…”

Neuronal Mitophagy: Friend or Foe?

“…Spermidine-treated aged-individuals displayed moderate improvement in the memory performance and enhanced mnemonic discrimination abilities compared to placebo-treated group (Wirth et al, 2018 ). The decreased levels of spermidine in blood serum of AD patients compared to healthy individuals, further support the therapeutic potential of polyamine-rich food supplementation against age-related dementia in humans (Madeo et al, 2018 ; Joaquim et al, 2019 ).…”

Non-linear association between serum spermidine and mild cognitive impairment: Results from a cross-sectional and longitudinal study

“…Contrastingly, in another 12-month randomized clinical trial, long-term SPD supplementation in participants with SCD did not modify memory performance and biomarkers compared with placebo ( Wirth et al, 2019 ). Additionally, Joaquim et al (2019) monitored their study participants for 4 years and found that SPD levels were lower in both patient groups Alzheimer’s disease (AD; MCI) than in healthy controls. Graham et al (2015) showed, through untargeted metabolomic analysis of human plasma, that polyamine metabolism was disrupted in patients with MCI.…”