Elevated spermidine serum levels in mild cognitive impairment, a potential biomarker of progression to Alzheimer dementia, a pilot study.

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There is a close link between iron and polyamine biosynthesis and metabolism. In a recent study, the authors reported alterations in the serum levels of hepcidin and other iron-related proteins in Alzheimer's disease patients. Hepcidin is a key regulator of the entry of iron into the circulation in mammals.

Iron plays a crucial role in many physiological processes of the human body. Early studies found iron overload is directly proportional to cognitive decline in Alzheimer's disease. Amyloid precursor protein (APP) and tau protein, both of which are related to the Alzheimer's disease pathogenesis, are associated with brain iron metabolism.

Polyamines are ubiquitous molecules, which, like iron, are essential for cell growth. All eukaryotic cells are equipped with a specific polyamine transport system (PTS). Polyamines have primary and secondary amino groups which chelate bivalent metal cations such as Fe and Cu.

Based on these findings, this pilot study compared serum levels of one of the polyamines, Spermidine, between Alzheimer's disease, mild cognitive impairment, and control subjects, correlating the levels with the existing clinical and neuroimaging data.

This cross-sectional study measured Spermidine levels in frozen serum samples of 43 Alzheimer's disease patients, 12 patients with Mild Cognitive Impairement (MCI) patients, and 21 age-matched controls, provided by the Oregon Alzheimer's Disease Center Bio-repository.

MCI patients showed significantly higher mean Spermidine serum levels compared to controls, with a non-significant trend for higher Spermidine serum levels in pure Alzheimer's disease participants compared to controls.

Furthermore, Spermidine serum levels correlated with serum levels of the chief iron regulatory protein, hepcidin in Alzheimer's disease participants with a more advanced disease stage.

These, and other results, demonstrate that the cell polyamine transport system is a potential cell entry pathway for iron. The studied polyamines, spermine and spermidine, may be components of the pool of transferrin-independent iron-chelating vectors, which have recently attracted the attention of many investigators.

Read the original article on Pubmed


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