Cerebrospinal fluid β2-microglobulin promotes the tau pathology through microglia–astrocyte communication in Alzheimer's disease

Alzheimer s Research & Therapy, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 2, 2025

Cerebrospinal fluid (CSF) β2-microglobulin (β2M) has been demonstrated as an important factor in β-amyloid (Aβ) neurotoxicity and a potential target for Alzheimer's disease (AD). However, more investigation is required to ascertain the relationship between β2M glial activities AD pathogenesis. In this study, 211 participants from Neuroimaging Initiative (ADNI) with CSF Plasma β2M, fibrillary acidic protein (GFAP), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), Aβ42, phosphorylated-tau (P-tau) total tau (T-tau) were divided into four groups, stage 0, 1, 2, suspected non-AD pathology (SNAP) based National Institute Aging- Association (NIA-AA) criteria. Multiple linear regression, mixed effects models, causal mediation analyses bootstrapped 10,000 iterations used investigate underlying associations among biomarkers at baseline during longitudinal visit. concentration decreased amyloid 1 compared 0 increased neurodegeneration SNAP 1. Moreover, level was positively correlated Aβ42 (β = 0.230), P-tau 0.564), T-tau 0.603), GFAP 0.552), sTREM2 0.641) (all P < 0.001). only longitudinally change. The correlation of (proportion 25.4%, 0.001) 26.7%, partially mediated by participants, reproduced late-life individuals. Furthermore, astrocyte cascade also pathological (β2M → YKL-40 P-tau/T-tau, IE: 0.424—0.435, all Nevertheless, not significant. Additionally, there no association plasma biomarkers. dynamic associated neuroinflammation. might mediate pathology, complementing existing research effect providing new perspective treatment.

Language: Английский

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The Role of Beta2-Microglobulin in Central Nervous System Disease

Cellular and Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 44(1)

Published: May 14, 2024

Abstract Central nervous system (CNS) disorders represent the leading cause of disability and second death worldwide, impose a substantial economic burden on society. In recent years, emerging evidence has found that beta2 -microglobulin (B2M), subunit major histocompatibility complex class I (MHC-I) molecules, plays crucial role in development progression certain CNS diseases. On one hand, intracellular B2M was abnormally upregulated brain tumors regulated tumor microenvironments progression. other soluble also elevated involved pathological stages Targeted therapy shown promising outcomes specific this review, we provide comprehensive summary discussion advances understanding processes involving diseases (e.g., Alzheimer's disease, aging, stroke, HIV-related dementia, glioma, primary central lymphoma).

Language: Английский

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β2-microglobulin and cognitive decline: unraveling the mediating role of the Dunedin Pace of Aging methylation

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: March 25, 2025

Background Progressive cognitive decline is inevitable with aging. Growing evidence links β2-microglobulin (B2M) to aging and decline. However, the current inadequate establish a definitive association. This study aims investigate relationship between B2M levels performance, together mediating effect of pace biological Methods Utilizing 1999–2002 National Health Nutrition Examination Survey (NHANES) database, performance was measured via Digit Symbol Substitution Test (DSST), while quantified using new generation DNA methylation algorithm, Dunedin Pace Aging (DunedinPoAm). Weighted multivariable linear regression used explore performance. Furthermore, subgroup analysis interaction tests were performed assess relationship’s stability. Mediation conducted DunedinPoAm on association Results The included 1,267 participants aged 60 over. After correcting for all confounders, each one-unit increment in log-transformed levels, DSST score fell by 5.13 points (95%CI −9.03 −1.24), level increased 0.04 0.01–0.07). trend test yielded identical results ( p &lt;0.05). Additionally, across every analyzed, correlation stable &gt;0.05). Further mediation showed that mediated 9.0% 0.1–43.2%) Conclusion These findings suggested substantial link elevated among U.S. older adults, partly through faster highlights potential as biomarker early detection therapeutic intervention aging-related

Language: Английский

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Associations of Epigenetic Age Estimators With Cognitive Function Trajectories in the Women's Health Initiative Memory Study

Neurology, Journal Year: 2024, Volume and Issue: 103(1)

Published: June 10, 2024

Epigenetic age estimators indicating faster/slower biological aging vs chronological independently associate with several age-related outcomes; however, longitudinal associations cognitive function are understudied. We examined of epigenetic measured annually.

Language: Английский

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Serum beta2-microglobulin acts as a biomarker for severity and prognosis in glioma patients: a preliminary clinical study

BMC Cancer, Journal Year: 2024, Volume and Issue: 24(1)

Published: June 6, 2024

Abstract Background Gliomas are the deadliest malignant tumors of adult central nervous system. We previously discovered that beta2-microglobulin (B2M) is abnormally upregulated in glioma tissues and it exerts a range oncogenic effects. Besides its tissue presence, serum B2M levels serve as biomarkers for various diseases. This study aimed to explore whether can be used diagnosis prognosis gliomas. Methods Medical records from 246 patients were retrospectively analyzed. The relationship between preoperative clinicopathological features was examined. Kaplan-Meier analysis, alongside uni- multivariate Cox regression, assessed association levels, systemic inflammatory markers, patient prognosis. Receiver operating characteristic (ROC) curve analysis evaluated diagnostic significance these specifically glioblastoma (GBM). Results Patients with gliomas exhibited elevated levels. Glioma high experienced shorter survival times. Multivariate determined (hazard ratio = 1.92, 95% confidence interval: 1.05–3.50, P 0.034) overall patients. demonstrated superior discriminatory power distinguishing GBM non-GBM compared inflammation indicators. Moreover, postoperative lower than majority Conclusions High correlated poor Serum shows promise novel biomarker predicting reflecting therapeutic response.

Language: Английский

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Menopause Hormone Replacement Therapy and Lifestyle Factors affect Metabolism and Immune System in the Serum Proteome of Aging Individuals

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 23, 2024

Abstract Aging is a fundamental risk factor for wide array of diseases. The Berlin Study II (BASE-II) cohort study designed to investigate the physical, mental, and social determinants successful aging. We utilized high-throughput mass spectrometry measure proteomes 1890 BASE-II participants, divided into two age groups: 27-37 years 60-85 years. employed multiple linear regression analyses explore effects demographic factors such as age, sex, BMI, along with hormonal treatments lifestyle factors, on serum proteome. identify new associations confirm previously described proteins linked BMI contraceptive use (HCU). Notably, we observed that abundance nutrient transport proteins, particularly apolipoproteins, metabolic diseases in aged individuals, including syndrome type 2 diabetes. Additionally, identified specific alterations explained by smoking alcohol consumption. further report significant proteome signature female participants corresponding menopause hormone replacement therapy (MHT). successfully classified these based MHT status an AUROC 0.82 using Complement Component 9 Plasminogen, slightly outperforming estradiol (AUROC: 0.80), active ingredient most preparations. Overall, our underscores impact therapies during aging, primarily affecting components immune system metabolism.

Language: Английский

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Plasma Proteomic Biomarkers in Alzheimer’s Disease and Cardiovascular Disease: A Longitudinal Study

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10751 - 10751

Published: Oct. 6, 2024

The co-occurrence of Alzheimer's disease (AD) and cardiovascular diseases (CVDs) in older adults highlights the necessity for exploration potential shared risk factors. A total 566 were selected from Disease Neuroimaging Initiative (ADNI) database, including 111 individuals with AD, 383 mild cognitive impairment (MCI), 410 CVD. multivariable linear mixed model (LMM) was used to investigate associations AD CVD longitudinal changes 146 plasma proteomic biomarkers (measured at baseline 12-month follow-up). LMM showed that 48 linked 46 (p < 0.05). Both associated 14 (α1Micro, ApoH, β2M, BNP, complement C3, cystatin C, KIM1, NGAL, PPP, TIM1, THP, TFF3, TM, VEGF), both MCI 12 (ApoD, AXL, Calcitonin, CD40, C-peptide, pM, TNFR2, TTR, suggesting intricate connections between decline health. Among these, Tamm Horsfall Protein (THP) MCI, CVD, APOE-ε4. This study provides valuable insights into distinct biological markers mechanisms underlying

Language: Английский

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Pomegranate Extract Administration Reverses Loss of Motor Coordination and Prevents Oxidative Stress in Cerebellum of Aging Mice

Antioxidants, Journal Year: 2023, Volume and Issue: 12(11), P. 1991 - 1991

Published: Nov. 11, 2023

The cerebellum is responsible for complex motor functions, like maintaining balance and stance, coordination of voluntary movements, learning, cognitive tasks. During aging, most these functions deteriorate, which results in falls accidents. aim this work was to elucidate the effect a standardized pomegranate extract during four months supplementation elderly mice prevent frailty improve oxidative state. Male C57Bl/6J eighteen-month-old were evaluated using "Valencia Score" at pre-supplementation post-supplementation periods. We analyzed lipid peroxidation brain cortex glutathione redox status peripheral blood. In addition, set aging-related genes apoptosis biomarkers measured via real-time polymerase chain reaction (RT-PCR). Our showed that improved skills aged coordination, neuromuscular function, monthly weight loss, but no changes grip strength endurance found. Furthermore, reversed increase malondialdehyde due aging increased reduced glutathione/oxidized (GSH/GSSG) ratio Finally, supplemented with not cerebral cortex.

Language: Английский

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Discovery of plasma biomarkers related to blood-brain barrier dysregulation in Alzheimer’s disease

Frontiers in Bioinformatics, Journal Year: 2024, Volume and Issue: 4

Published: Oct. 4, 2024

Introduction Blood-based biomarkers are quantitative, non-invasive diagnostic tools. This study aimed to identify candidate for Alzheimer’s disease (AD) using publicly available omics datasets, the hypothesis that with blood-brain barrier dysfunction in AD, brain-synthesized proteins can leak into plasma detection. Methods Differential abundance results of and brain proteomic datasets were integrated obtain a list potential biomarkers. Biological validity was investigated intercellular communication gene regulatory analyses on single-cell transcriptomics data. Results Five (APOD, B2M, CFH, CLU, C3) fit biomarker criteria. 4 corresponding transcripts overexpressed AD astrocytes, mediated by AD-related dysregulations transcription factors regulating neuroinflammation. Additionally, CLU specifically induced downstream expression neuronal death genes. Discussion In conclusion, 5-protein panel is shown effectively patients, evidence specificity biological validity. Future research should investigate mechanism protein leakage through barrier.

Language: Английский

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