ABSTRACT
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.
Subject(s)
Humans , Male , Female , Aged , Aged, 80 and over , Polyamines/blood , Spermine/blood , Alzheimer Disease/physiopathology , Cognitive Dysfunction/physiopathology , Ornithine/blood , Polyamines/metabolism , Biomarkers/blood , Putrescine/blood , Spermidine/blood , Chromatography, Liquid/methods , Tandem Mass Spectrometry/methods , Metabolomics/methods , Alzheimer Disease/diagnosis , Cognitive Dysfunction/diagnosisABSTRACT
Spermidine [spd] oxidase was initially purified from sera of schizophrenic and normal subjects by anion exchange chromatography. This purified the spd oxidase 105 and 128 folds, relative to the crude sera of schizophrenics and normals respectively. The specific activities of purified Spd oxidase were 231.3 and 135.2 nkat/mg protein, for schizophrenic and normal respectively. Spermidine oxidase activity was found to be linearly proportional to the amount of protein up to 900 micro g and with time of reaction up to about 50 sec. The enzyme showed a maximum activity at PH 4.5 for both schizophrenic and normal subjects. Spermidine oxidase was found to be highly activated by Ca++, ospexin and to a lesser extent, by Al+++ and folic acid. While the activity of this enzyme was found to be inhibited highly by pyrazole, antipyrine, iodoacetamide, glutathione and Inderal