Thinking outside the black box: are the brain endothelial cells the new main target in Alzheimer's disease?

The blood-brain barrier is the interface through which the brain interacts with the milieu and consists mainly of a sophisticated network of brain endothelial cells that forms blood vessels and selectively moves molecules inside and outside the brain through multiple mechanisms of transport. Although brain endothelial cell function is crucial for brain homeostasis, their role in neurodegenerative diseases has historically not been considered with the same importance as other brain cells such as microglia, astroglia, neurons, or even molecules such as amyloid beta, Tau, or alpha-synuclein. Alzheimer's disease is the most common neurodegenerative disease, and brain endothelial cell dysfunction has been reported by several groups. However, its impairment has barely been considered as a potential therapeutic target. Here we review the most recent advances in the relationship between Alzheimer's disease and brain endothelial cells commitment and analyze the possible mechanisms through which their alterations contribute to this neurodegenerative disease, highlighting their inflammatory phenotype and the possibility of an impaired secretory pattern of brain endothelial cells that could contribute to the progression of this ailment. Finally, we discuss why shall brain endothelial cells be appreciated as a therapeutic target instead of solely an obstacle for delivering treatments to the injured brain in Alzheimer's disease.

A diagnostic model for overweight and obesity from untargeted urine metabolomics of soldiers.

Soldiers in active military service need optimal physical fitness for successfully carrying out their operations. Therefore, their health status is regularly checked by army doctors. These inspections include physical parameters such as the body-mass index (BMI), functional tests, and biochemical studies. If a medical exam reveals an individual's excess weight, further examinations are made, and corrective actions for weight lowering are initiated. The collection of urine is non-invasive and therefore attractive for frequent metabolic screening. We compared the chemical profiles of urinary samples of 146 normal weight, excess weight, and obese soldiers of the Mexican Army, using untargeted metabolomics with liquid chromatography coupled to high-resolution mass spectrometry (LC-MS). In combination with data mining, statistical and metabolic pathway analyses suggest increased S-adenosyl-L-methionine (SAM) levels and changes of amino acid metabolites as important variables for overfeeding. We will use these potential biomarkers for the ongoing metabolic monitoring of soldiers in active service. In addition, after validation of our results, we will develop biochemical screening tests that are also suitable for civil applications.