Biomarkers of neuroinflammation and microcirculatory dysfunction in Alzheimer's disease: a comprehensive assessment of the pathogenetic and diagnostic role

Medical alphabet, Journal Year: 2025, Volume and Issue: 2, P. 29 - 38

Published: March 27, 2025

The aim of the study was to identify laboratory biomarkers asthma that could be promising for research as diagnostic tools. Materials and methods . 52 patients with 59 in control group without cognitive impairment were examined, which concentration 103 potential blood plasma (111 people) CSF (24 studied. Results Statistically significant differences (p<0.01) concentrations 43 obtained group. In a correlation matrix reflecting interactions between (17 markers) (13 markers). Conclusion. Our results indicate role neuroinflammation, vascular pathology, angiogenesis, BBB dysfunction pathological process occurring asthma, previously confirmed by various researchers. Pathogenetically based associated links pathogenesis have been identified. Biomarkers lipid metabolism, such Apo-A1, Apo-CII peripheral bloodstream can considered indicators vascular-neurodegenerative process. Pro-inflammatory cytokines (IFNa, IFNy, IL-15, IL-1a, IL-8, sTNFR-1, sTNFR-2, IL-12p70 (including its IL-12p40 subunit), IL-17a, sCD 40L, sgp130, IP10, endoglin) anti-inflammatory (G-CSF1, BMP9, complement C 4, D-dimer, EFG1, eotaxin, fractalkine, G-CSF, GM–CSF, GDF-15, IL-1RA, IL-4, MDC, MIP1 β, MIP4, P-selectin, PEDF, 30, sICAM-1, sNCAM-1, sIL-2ra, sIL-4r, TGFa VEGF-C, alpha-1-antitrypsin) plasma, they are candidates future effective biomarkers. most biomarker seems interleukin 12 subunit 40 (IL-12p40), due increase contrast greatest number correlations level other CSF.

Language: Английский

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New Insights into Microglial Mechanisms of Memory Impairment in Alzheimer’s Disease

Biomolecules, Journal Year: 2022, Volume and Issue: 12(11), P. 1722 - 1722

Published: Nov. 21, 2022

Alzheimer’s disease (AD) is the most common progressive and irreversible neurodegeneration characterized by impairment of memory cognition. Despite years studies, no effective treatment prevention strategies are available yet. Identifying new AD therapeutic targets crucial for better elucidating pathogenesis establishing a valid AD. Growing evidence suggests that microglia play critical role in Microglia resident macrophages central nervous system (CNS), their core properties supporting main biological functions include surveillance, phagocytosis, release soluble factors. Activated not only directly mediate immune response, but also participate pathological changes AD, including amyloid-beta (Aβ) aggregation, tau protein phosphorylation, synaptic dissection, neuron loss, function decline, etc. Based on these recent findings, we provide framework to summarize impairment. This have potential become therapy.

Language: Английский

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Development of nanomedicines for the treatment of Alzheimer’s disease: Raison d’être, strategies, challenges and regulatory aspects

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 98, P. 102318 - 102318

Published: May 4, 2024

Language: Английский

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Residual microglia following short‐term PLX5622 treatment in 5xFAD mice exhibit diminished NLRP3 inflammasome and mTOR signaling, and enhanced autophagy

Aging Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 21, 2024

Abstract While moderately activated microglia in Alzheimer's disease (AD) are pivotal clearing amyloid beta (Aβ), hyperactivated perpetuate neuroinflammation. Prior investigations reported that the elimination of ~80% through inhibition colony‐stimulating factor 1 receptor (CSF1R) during advanced stage neuroinflammation 5xFamilial AD (5xFAD) mice mitigates synapse loss and neurodegeneration. Furthermore, prolonged CSF1R diminished development parenchymal plaques. Nonetheless, effects short‐term early stages on residual unknown. Therefore, we investigated 10‐day using PLX5622 three‐month‐old female 5xFAD mice, a characterized by onset minimal Aβ We observed ~65% depletion hippocampus cerebral cortex. The leftover displayed noninflammatory phenotype with reduced NOD‐, LRR‐, pyrin domain‐containing protein 3 (NLRP3) inflammasome complexes. Moreover, plaque‐associated were Clec7a expression. Additionally, phosphorylated S6 ribosomal sequestosome analysis suggested mechanistic targets rapamycin (mTOR) signaling autophagy neurons within Biochemical assays validated NLRP3 activation, decreased mTOR cortex, enhanced hippocampus. However, did not influence plaques, soluble Aβ‐42 levels, astrocyte hypertrophy, or hippocampal neurogenesis. Thus, promotes retention homeostatic activation signaling, alongside increased autophagy.

Language: Английский

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Cerebrospinal fluid inflammatory biomarkers for disease progression in Alzheimer’s disease and multiple sclerosis: a systematic review

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 13, 2023

Inflammatory processes are involved in the pathophysiology of both Alzheimer’s disease (AD) and multiple sclerosis (MS) but their exact contribution to progression remains be deciphered. Biomarkers needed define pathophysiological these disorders, who may increasingly co-exist elderly generations future, due rising prevalence ameliorated treatment options with improved life expectancy MS. The purpose this review was provide a systematic overview inflammatory biomarkers, as measured cerebrospinal fluid (CSF), that associated clinical progression. International peer-reviewed literature screened using PubMed Web Science databases. Disease had clinically validated tests representing baseline functional and/or cognitive status, evolution such scores over time transitioning from one stage more severe stage. quality included studies systematically evaluated set questions for clinical, neurochemical statistical characteristics study. A total 84 papers were (twenty-five AD 59 MS). Elevated CSF levels chitinase-3-like protein 1 (YKL-40) Osteopontin monocyte chemoattractant protein-1 specifically related AD, whereas same true interleukin-1 beta, tumor necrosis factor alpha, C-X-C motif ligand 13, glial fibrillary acidic IgG oligoclonal bands We observed broad heterogeneity varying cohort characterization, non-disclosure measures analyses lack adequate longitudinal designs. Most retrieved biomarkers innate immune system activity, which seems an important mediator Overall study limited we have framed some recommendations future biomarker research field. Systematic registration https://www.crd.york.ac.uk/prospero/ , identifier CRD42021264741.

Language: Английский

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Transformation of non-neuritic into neuritic plaques during AD progression drives cortical spread of tau pathology via regenerative failure

Acta Neuropathologica Communications, Journal Year: 2023, Volume and Issue: 11(1)

Published: Dec. 1, 2023

Extracellular amyloid-β (Aβ) plaques and intracellular aggregates of tau protein in form neurofibrillary tangles (NFT) are pathological hallmarks Alzheimer's disease (AD). The exact mechanism how these two interact AD is still a matter debate. Neuritic (NP), subset Aβ containing dystrophic neurites (DN), suggested to be unique might play role the interaction tau. Quantifying NP non-NP postmortem brain specimens from patients with increasing severity neuropathological changes (ADNC), we demonstrate that total number increase, while stagnates. Furthermore, investigating correlation between NFT, identified unexpected region-specific differences when comparing cases increasingly more severe ADNC. In neocortical regions NFT counts increase parallel during progression ADNC, this not observed hippocampus. These data support notion transformed into ADNC indicate drive cortical formation. Next, using spatial transcriptomics, analyzed gene expression profile microenvironment around NP. We an upregulation neuronal systems Ca-dependent event pathways compared non-NP. speculate transcripts may hint at compensatory underlying Our studies suggest transformation key points regenerative failure as potential driving force process.

Language: Английский

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Alzheimer’s Disease, Obesity, and Type 2 Diabetes: Focus on Common Neuroglial Dysfunctions (Critical Review and New Data on Human Brain and Models)

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(11), P. 1101 - 1101

Published: Oct. 30, 2024

Obesity, type 2 diabetes (T2D), and Alzheimer's disease (AD) are pathologies that affect millions of people worldwide. They have no effective therapy difficult to prevent control when they develop. It has been known for many years these diseases pathogenic aspects in common. We highlight this review neuroglial cells (astroglia, oligodendroglia, microglia) play a vital role the origin, clinical-pathological development, course brain neurodegeneration. Moreover, we include new results T2D-AD mouse model (APP+PS1 mice on high-calorie diet) investigating.

Language: Английский

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D-beta-hydroxybutyrate protects against microglial activation in lipopolysaccharide-treated mice and BV-2 cells

Metabolic Brain Disease, Journal Year: 2022, Volume and Issue: 38(3), P. 1115 - 1126

Published: Dec. 22, 2022

Language: Английский

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The brain pathobiome in Alzheimer's disease

Neurotherapeutics, Journal Year: 2024, Volume and Issue: 21(6), P. e00475 - e00475

Published: Oct. 1, 2024

Language: Английский

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Transplanting Microglia for Treating CNS Injuries and Neurological Diseases and Disorders, and Prospects for Generating Exogenic Microglia

Cell Transplantation, Journal Year: 2023, Volume and Issue: 32

Published: Jan. 1, 2023

Microglia are associated with a wide range of both neuroprotective and neuroinflammatory functions in the central nervous system (CNS) during development throughout lifespan. Chronically activated dysfunctional microglia found many diseases disorders, such as Alzheimer’s disease, Parkinson’s CNS-related injuries, can accelerate or worsen condition. Transplantation studies designed to replace supplement healthy offer promising strategy for addressing microglia-mediated neuroinflammation pathologies. This review will cover microglial involvement neurological disorders current transplantation strategies, different approaches considerations generating exogenic microglia.

Language: Английский

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