Circulating arginine metabolites in Alzheimer’s disease and vascular dementia: A systematic review and meta-analysis

Zinellu, Angelo; Tommasi, Sara; Sedda, Stefania; Mangoni, Arduino A.

doi:10.1016/j.arr.2023.102139

Cited by 2 publications

(2 citation statements)

References 89 publications

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“…Tight junctions between cerebral endothelial cells play an important role in the function of the BBB, and recent studies have demonstrated the essential role of microRNAs in regulating tight junctions [27]. Recently, the brain-derived neurotrophic factor (BDNF) and circulating arginine metabolites were suggested as potential biomarkers of Alzheimer's disease (AD) [28,29]. Numerous recent studies have indicated that vascular risk factors are associated with various forms of dementia and that most forms of dementia can be considered an extension of vascular disease.…”

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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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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“…Recently researchers have found that amino acid homeostasis is disrupted in the serum and brain of patients with AD (Trushina et al, 2013 ; Lin et al, 2018 ; Wang et al, 2021 ; Li et al, 2022 ; Zinellu et al, 2023 ). Moreover, alterations in the levels of different amino acids in the physiological range have been linked to various pathological conditions, including neurological disorders (Kepka et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Systems genetics identifies methionine as a high risk factor for Alzheimer's disease

Wang,

Hei,

Liu

et al. 2024

Front. Neurosci.

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As a dietary strategy, methionine restriction has been reported to promote longevity and regulate metabolic disorders. However, the role and possible regulatory mechanisms underlying methionine in neurodegenerative diseases such as Alzheimer's disease (AD), remain unexplored. This study utilized the data from BXD recombinant inbred (RI) mice to establish a correlation between the AD phenotype in mice and methionine level. Gene enrichment analysis indicated that the genes associated with the concentration of methionine in the midbrain are involved in the dopaminergic synaptic signaling pathway. Protein interaction network analysis revealed that glycogen synthase kinase 3 beta (GSK-3β) was a key regulator of the dopaminergic synaptic pathway and its expression level was significantly correlated with the AD phenotype. Finally, in vitro experiments demonstrated that methionine deprivation could reduce the expression of Aβ and phosphorylated Tau, suggesting that lowering methionine levels in humans may be a preventive or therapeutic strategy for AD. In conclusion, our findings support that methionine is a high risk factor for AD. These findings predict potential regulatory network, theoretically supporting methionine restriction to prevent AD.

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Circulating arginine metabolites in Alzheimer’s disease and vascular dementia: A systematic review and meta-analysis

Cited by 2 publications

References 89 publications

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

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

Systems genetics identifies methionine as a high risk factor for Alzheimer's disease

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