COVID-19 and Alzheimer's Disease: Neuroinflammation, Oxidative Stress, Ferroptosis, and Mechanisms Involved.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by marked cognitive decline, memory loss, and spatio-temporal troubles and, in severe cases, lack of recognition of family members. Neurological symptoms, cognitive disturbances, and the inflammatory frame due to COVID-19, together with long-term effects, have fueled renewed interest in AD based on similar damage. COVID-19 also caused the acceleration of AD symptom onset. In this regard, the morbidity and mortality of COVID-19 were reported to be increased in patients with AD due to multiple pathological changes such as excessive expression of the viral receptor angiotensin-converting enzyme 2 (ACE2), comorbidities such as diabetes, hypertension, or drug-drug interactions in patients receiving polypharmacy and the high presence of proinflammatory molecules. Furthermore, the release of cytokines, neuroinflammation, oxidative stress, and ferroptosis in both diseases showed common underlying mechanisms, which together worsen the clinical picture and prognosis of these patients.

Neuroproteomics Chip-Based Mass Spectrometry and Other Techniques for Alzheimer's Disease Biomarkers - Update.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease of growing interest given that there is cognitive damage and symptom onset acceleration. Therefore, it is important to find AD biomarkers for early diagnosis, disease progression, and discrimination of AD and other diseases. OBJECTIVE: The objective of this study is to update the relevance of mass spectrometry for the identification of peptides and proteins involved in AD useful as discriminating biomarkers. METHODS: Proteomics and peptidomics technologies that show the highest possible specificity and selectivity for AD biomarkers are analyzed, together with the biological fluids used. In addition to positron emission tomography and magnetic resonance imaging, MALDI-TOF mass spectrometry is widely used to identify proteins and peptides involved in AD. The use of protein chips in SELDI technology and electroblotting chips for peptides makes feasible small amounts (µL) of samples for analysis. RESULTS: Suitable biomarkers are related to AD pathology, such as intracellular neurofibrillary tangles; extraneuronal senile plaques; neuronal and axonal degeneration; inflammation and oxidative stress. Recently, peptides were added to the candidate list, which are not amyloid-ß or tau fragments, but are related to coagulation, brain plasticity, and complement/neuroinflammation systems involving the neurovascular unit. CONCLUSION: The progress made in the application of mass spectrometry and recent chip techniques is promising for discriminating between AD, mild cognitive impairment, and matched healthy controls. The application of this technique to blood samples from patients with AD has shown to be less invasive and fast enough to determine the diagnosis, stage of the disease, prognosis, and follow-up of the therapeutic response.

Uncommon Noninvasive Biomarkers for the Evaluation and Monitoring of the Etiopathogenesis of Alzheimer's Disease.

BACKGROUND: Alzheimer´s disease (AD) is the most widespread dementia in the world, followed by vascular dementia. Since AD is a heterogeneous disease that shows several varied phenotypes, it is not easy to make an accurate diagnosis, so it arises when the symptoms are clear and the disease is already at an advanced stage. Therefore, it is important to find out biomarkers for early AD diagnosis that facilitate treatment or slow down the disease. Classic biomarkers are obtained from cerebrospinal fluid and plasma, along with brain imaging by positron emission tomography. Attempts have been made to discover uncommon biomarkers from other body fluids, which are addressed in this update. OBJECTIVE: This update aims to describe recent biomarkers from minimally invasive body fluids for the patients, such as saliva, urine, eye fluid or tears. METHODS: Biomarkers were determined in patients versus controls by single tandem mass spectrometry and immunoassays. Metabolites were identified by nuclear magnetic resonance and microRNAs with genome-wide high-throughput real-time polymerase chain reaction-based platforms. RESULTS: Biomarkers from urine, saliva, and eye fluid were described, including peptides/proteins, metabolites, and some microRNAs. The association with AD neuroinflammation and neurodegeneration was analyzed, highlighting the contribution of matrix metalloproteinases, the immune system and microglia, as well as the vascular system. CONCLUSION: Unusual biomarkers have been developed, which distinguish each stage and progression of the disease, and are suitable for the early AD diagnosis. An outstanding relationship of biomarkers with neuroinflammation and neurodegeneration was assessed, clearing up concerns about the etiopathogenesis of AD.

In vivo long-term kinetics of radiolabeled n,n-dimethyltryptamine and tryptamine.

UNLABELLED: N,N-dimethyltryptamine (DMT), a strong psychodysleptic drug, has been found in higher plants, shamanic hallucinogenic beverages, and the urine of schizophrenic patients. The aim of this work was to gain better knowledge on the relationship between this drug and hallucinogenic processes by studying DMT behavior in comparison with tryptamine. METHODS: (131)I-labeled DMT and tryptamine were injected into rabbits. γ-Camera and biodistribution studies were performed. Brain uptake, plasma clearance, and renal excretion were assessed for each indolealkylamine. RESULTS: DMT and tryptamine showed different behavior when brain uptake, residence time, and excretion were compared. Labeled DMT entered the brain 10 s after injection, crossed the blood-brain barrier, and bound to receptors; then it was partially renally excreted. It was detected in urine within 24 h after injection and remained in the brain, even after urine excretion ceased; up to 0.1% of the injected dose was detected at 7 d after injection in the olfactory bulb. In contrast, tryptamine was rapidly taken up in the brain and fully excreted 10 min after injection. CONCLUSION: To our knowledge, this is the first demonstration that exogenous DMT remains in the brain for at least 7 d after injection. Although labeled DMT and tryptamine behave as agonists for at least 5-hydroxytryptamine 2A receptor, 5-hydroxytryptamine 2C receptor, trace amine-associated receptor, and σ-1 putative receptor targets, binding to the latter can explain the different behavior of labeled DMT and tryptamine in the brain. The persistence in the brain can be further explained on the basis that DMT and other N,N-dialkyltryptamines are transporter substrates for both the plasma membrane serotonin transporter and the vesicle monoamine transporter 2. Furthermore, storage in vesicles prevents DMT degradation by monoamine oxidase. At high concentrations, DMT is taken up by the serotonin transporter and further stored in vesicles by the vesicle monoamine transporter 2, to be released under appropriate stimuli. Moreover, the (131)I-labeling proved to be a useful tool to perform long-term in vivo studies.

High-performance capillary electrophoresis analysis of mate infusions prepared from stems and leaves of Ilex paraguariensis using automated micellar electrokinetic capillary chromatography.

An automated micellar electrokinetic capillary chromatographic method has been developed in order to determine xanthines, e.g. caffeine, theobromine and theophylline, and chlorogenic acid in samples of yerba mate (Ilex paraguariensis). The target constituents were detected by photodiode array, and quantified by an external standard method. In addition, each constituent was collected separately and identified by EIMS. The method has been used to analyse 30 samples of mate infusions prepared at 30 and 75 degrees C with milled leaves and stems of 14 commercial brands which had been subjected to different elaboration processes. Suspended powdered material of each infusion was also analysed after three sieving steps. There was a remarkable difference in the relative xanthine composition of the finely suspended material, the amount of which varied according to the yerba mate brand, the elaboration process and the temperature of the infusion. The importance of these results with respect to gastrointestinal disorders which have been observed by habitual consumers of mate are discussed.

Método rápido y sensible para detectar aminas primarias y secundarias no fenólicas en orina humana / A fast and sensitive method to detect primary and secondary non-phenolic amines in human urine

En este trabajo se desarrolló una metodología cromatográfica rápida y precisa para buscar aminas primarias y secundarias O-metiladas, típicas de ciertos desórdenes mentales, en muestras de orina humanas de 24 horas. La extracción de la orina fue llevada a cabo bajo condiciones alcalinas para evitar la interferencia de catecolaminas y ácidos urinarios. Después de la extracción alcalina, a cada muestra se la hizo reaccionar con cloruro de dansilo en acetonitrilo en presencia de bicarbonato de sodio en exceso, para formar las correspondientes dansilamidas. Las fenetilamidas y las indolalquilaminas O-metiladas fueron visualizadas en placas de fase reversa de alta resolución (HP-TLC), por cromatografía líquida de alta resolución (HPLC) y por cromatografía gas-líquido (CGL) y, además, fueron identificadas por cromatografía gas-líquido acoplada con espectrometría de masas (CGL-EM). Este método es lo suficientemente sensible para estos metabolitos en muestras de orina y, por lo tanto, resulta útil para investigaciones biomédicas y clínicas de aminas primarias y secundarias no fenólicas en orina

Método rápido y sensible para detectar aminas primarias y secundarias no fenólicas en orina humana / A fast and sensitive method to detect primary and secondary non-phenolic amines in human urine

En este trabajo se desarrolló una metodología cromatográfica rápida y precisa para buscar aminas primarias y secundarias O-metiladas, típicas de ciertos desórdenes mentales, en muestras de orina humanas de 24 horas. La extracción de la orina fue llevada a cabo bajo condiciones alcalinas para evitar la interferencia de catecolaminas y ácidos urinarios. Después de la extracción alcalina, a cada muestra se la hizo reaccionar con cloruro de dansilo en acetonitrilo en presencia de bicarbonato de sodio en exceso, para formar las correspondientes dansilamidas. Las fenetilamidas y las indolalquilaminas O-metiladas fueron visualizadas en placas de fase reversa de alta resolución (HP-TLC), por cromatografía líquida de alta resolución (HPLC) y por cromatografía gas-líquido (CGL) y, además, fueron identificadas por cromatografía gas-líquido acoplada con espectrometría de masas (CGL-EM). Este método es lo suficientemente sensible para estos metabolitos en muestras de orina y, por lo tanto, resulta útil para investigaciones biomédicas y clínicas de aminas primarias y secundarias no fenólicas en orina (AU)