The Other Side of Alzheimer’s Disease: Influence of Metabolic Disorder Features for Novel Diagnostic Biomarkers

Argentati, Chiara; Tortorella, Ilaria; Bazzucchi, Martina; Emiliani, Carla; Morena, Francesco; Martino, Sabata

doi:10.3390/jpm10030115

Cited by 8 publications

(5 citation statements)

References 352 publications

(436 reference statements)

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“…Interestingly, it has been shown that genetic variations of the gene encoding the CYP2C8 drug metabolizing enzymes can lead to clinical differences in drug metabolism and ultimately variations in drug effectiveness and toxicities within populations in the same country. This is observed in different populations living in Jordan [ 21 ], which include Chechens (~1%) and Circassians, genetically isolated groups [ 22 , 23 ]. Chechens display several pharmacogenomics variants (i.e ABCB1 , VDR ) resembling those present in Europeans and Finnish [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenomic profile of a central European urban random population-Czech population

et al. 2023

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The genetic basis of variability in drug response is at the core of pharmacogenomics (PGx) studies, aiming at reducing adverse drug reaction (ADR), which have interethnic variability. This study used the Kardiovize Brno 2030 random urban Czech sample population to analyze polymorphisms in a wide spectrum of genes coding for liver enzymes involved in drug metabolism. We aimed at correlating real life drug consumption with pharmacogenomic profile, and at comparing these data with the SUPER-Finland Finnish PGx database. A total of 250 individuals representative of the Kardiovize Brno 2030 cohort were included in an observational study. Blood DNA was extracted and 59 single nucleotide polymorphisms within 13 genes (BCHE, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A5, F2, F5, IFNL3, SLCO1B1, TPMT, UGT1A1, VKORC1), associated to different drug metabolizing rates, were characterized by genotyping using a genome wide commercial array. Widely used drugs such as anti-coagulant warfarin and lipid lowering agent atorvastatin were associated to an alarmingly high percentage of users with intermediate/poor metabolism for them. Significant differences in the frequency of normal/intermediate/poor/ultrarapid/rapid metabolizers were observed for CYPD26 (p<0.001), CYP2C19 (p<0.001) and UGT1A1 (p<0.001) between the Czech and the Finnish study populations. Our study demonstrated that administration of some popular drugs to a Czech random sample population is associated with different drug metabolizing rates and therefore exposing to risk for ADRs. We also highlight interethnic differentiation of some common pharmacogenetics variants between Central (Czech) and North European (Finnish) population studies, suggesting the utility of PGx-informed prescription based on variant genotyping.

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Section: Discussionmentioning

confidence: 99%

Pharmacogenomic profile of a central European urban random population-Czech population

et al. 2023

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“…Over the last two decades, evidence has accumulated demonstrating how the physico-chemical properties of the cellular microenvironment, as well as the physical forces exerted by cells and tissues, are critical in the regulation of physiological conditions (such as tissue development, repair, and homeostasis, cell motility, proliferation, metabolism and differentiation) (Mammoto and Ingber 2010 ; Morena et al 2017 , 2020 ; Argentati et al 2018 , 2019 ; Wolfenson et al 2019 ) but also pathological states (Jansen et al 2015 ; Jensen et al 2015 ; Alcaraz et al 2018 ; Kim et al 2019 ; Lee et al 2019 ; Argentati et al 2019 , 2020b ; Hall et al 2020 ). In both contexts, cells must adapt their behavior using their capability to sense the external physical forces— mechanosensing —and to transduce these forces into biochemical signals— mechanotransduction (Trubelja and Bao 2018 ; Martino et al 2018 ; Argentati et al 2019 ).…”

Section: Organoids and Mechanobiologymentioning

confidence: 99%

The role of physical cues in the development of stem cell-derived organoids

et al. 2021

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Organoids are a novel three-dimensional stem cells’ culture system that allows the in vitro recapitulation of organs/tissues structure complexity. Pluripotent and adult stem cells are included in a peculiar microenvironment consisting of a supporting structure (an extracellular matrix (ECM)-like component) and a cocktail of soluble bioactive molecules that, together, mimic the stem cell niche organization. It is noteworthy that the balance of all microenvironmental components is the most critical step for obtaining the successful development of an accurate organoid instead of an organoid with heterogeneous morphology, size, and cellular composition. Within this system, mechanical forces exerted on stem cells are collected by cellular proteins and transduced via mechanosensing—mechanotransduction mechanisms in biochemical signaling that dictate the stem cell specification process toward the formation of organoids. This review discusses the role of the environment in organoids formation and focuses on the effect of physical components on the developmental system. The work starts with a biological description of organoids and continues with the relevance of physical forces in the organoid environment formation. In this context, the methods used to generate organoids and some relevant published reports are discussed as examples showing the key role of mechanosensing–mechanotransduction mechanisms in stem cell-derived organoids.

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“…Besides genetically determined factors, in addition to acute environmental factors, all people experience age-related changes in blood vessels over time, which can become an independent cause of neurodegenerative diseases. The main diseases, in terms of scale and worldwide distribution, are senile dementia of the Alzheimer's type or sporadic Alzheimer's disease (SAD) which accounts for 85-90% of total patients [8][9][10]. Further, an important emerging avenue in dementia research is understanding the vascular contributors to dementia.…”

Section: Introductionmentioning

confidence: 99%

Immunological Profile and Markers of Endothelial Dysfunction in Elderly Patients with Cognitive Impairments

Goncharov,

Popova,

Kudryavtsev

et al. 2024

IJMS

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The process of aging is accompanied by a dynamic restructuring of the immune response, a phenomenon known as immunosenescence. Further, damage to the endothelium can be both a cause and a consequence of many diseases, especially in elderly people. The purpose of this study was to carry out immunological and biochemical profiling of elderly people with acute ischemic stroke (AIS), chronic cerebral circulation insufficiency (CCCI), prediabetes or newly diagnosed type II diabetes mellitus (DM), and subcortical ischemic vascular dementia (SIVD). Socio-demographic, lifestyle, and cognitive data were obtained. Biochemical, hematological, and immunological analyses were carried out, and extracellular vesicles (EVs) with endothelial CD markers were assessed. The greatest number of significant deviations from conditionally healthy donors (HDs) of the same age were registered in the SIVD group, a total of 20, of which 12 were specific and six were non-specific but with maximal differences (as compared to the other three groups) from the HDs group. The non-specific deviations were for the MOCA (Montreal Cognitive Impairment Scale), the MMSE (Mini Mental State Examination) and life satisfaction self-assessment scores, a decrease of albumin levels, and ADAMTS13 (a Disintegrin and Metalloproteinase with a Thrombospondin Type 1 motif, member 13) activity, and an increase of the VWF (von Willebrand factor) level. Considering the significant changes in immunological parameters (mostly Th17-like cells) and endothelial CD markers (CD144 and CD34), vascular repair was impaired to the greatest extent in the DM group. The AIS patients showed 12 significant deviations from the HD controls, including three specific to this group. These were high NEFAs (non-esterified fatty acids) and CD31 and CD147 markers of EVs. The lowest number of deviations were registered in the CCCI group, nine in total. There were significant changes from the HD controls with no specifics to this group, and just one non-specific with a maximal difference from the control parameters, which was α1-AGP (alpha 1 acid glycoprotein, orosomucoid). Besides the DM patients, impairments of vascular repair were also registered in the CCCI and AIS patients, with a complete absence of such in patients with dementia (SIVD group). On the other hand, microvascular damage seemed to be maximal in the latter group, considering the biochemical indicators VWF and ADAMTS13. In the DM patients, a maximum immune response was registered, mainly with Th17-like cells. In the CCCI group, the reaction was not as pronounced compared to other groups of patients, which may indicate the initial stages and/or compensatory nature of organic changes (remodeling). At the same time, immunological and biochemical deviations in SIVD patients indicated a persistent remodeling in microvessels, chronic inflammation, and a significant decrease in the anabolic function of the liver and other tissues. The data obtained support two interrelated assumptions. Taking into account the primary biochemical factors that trigger the pathological processes associated with vascular pathology and related diseases, the first assumption is that purine degradation in skeletal muscle may be a major factor in the production of uric acid, followed by its production by non-muscle cells, the main of which are endothelial cells. Another assumption is that therapeutic factors that increase the levels of endothelial progenitor cells may have a therapeutic effect in reducing the risk of cerebrovascular disease and related neurodegenerative diseases.

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The Other Side of Alzheimer’s Disease: Influence of Metabolic Disorder Features for Novel Diagnostic Biomarkers

Cited by 8 publications

References 352 publications

Pharmacogenomic profile of a central European urban random population-Czech population

Pharmacogenomic profile of a central European urban random population-Czech population

The role of physical cues in the development of stem cell-derived organoids

Immunological Profile and Markers of Endothelial Dysfunction in Elderly Patients with Cognitive Impairments

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