The cerebrospinal fluid interleukin 8 (IL‐8) concentration in Alzheimer’s disease (AD)

Doroszkiewicz, Julia; Kulczyńska-Przybik, Agnieszka; Dulewicz, Maciej; Borawska, Renata; Krawiec, Anita; Słowik, Agnieszka; Mroczko, Barbara

doi:10.1002/alz.051317

Cited by 6 publications

(4 citation statements)

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“…IL-1α plays a crucial role in AD pathogenesis, particularly the homozygosity for a specific IL-1α gene polymorphism at least triples the risk for the development of AD (reviewed in [ 44 ]). Again, studies in cultured human microglia display a significant role of interleukin-8 in neuroinflammation, and literature data indicate that gene polymorphism in IL-8 may affect the predisposition of AD [ 45 ]. Indeed, it has been demonstrated that micro vessels derived from AD brain express high levels of MIP-1α mRNA as well as release high levels of MIP-1α protein when compared with brain micro vessels isolated from cognitively healthy controls.…”

Section: Discussionmentioning

confidence: 99%

miRNAs and Alzheimer’s Disease: Exploring the Role of Inflammation and Vitamin E in an Old-Age Population

et al. 2023

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Alzheimer’s disease (AD) is the most frequent cause of dementia worldwide and represents one of the leading factors for severe disability in older persons. Although its etiology is not fully known yet, AD may develop due to multiple factors, including inflammation and oxidative stress, conditions where microRNAs (miRNAs) seem to play a pivotal role as a molecular switch. All these aspects may be modulated by nutritional factors. Among them, vitamin E has been widely studied in AD, given the plausibility of its various biological functions in influencing neurodegeneration. From a cohort of old-aged people, we measured eight vitamin E forms (tocopherols and tocotrienols), thirty cytokines/chemokines, and thirteen exosome-extracted miRNAs in plasma of subjects suffering from subjects affected by AD and age-matched healthy controls (HC). The sample population included 80 subjects (40 AD and 40 HC) with a mean age of 77.6 ± 3.8 years, mostly women (45; 56.2%). Of the vitamin E forms, only α-tocopherol differed between groups, with significantly lower levels in AD. Regarding the examined inflammatory molecules, G-CSF, GM-CSF, INF-α2, IL-3, and IL-8 were significantly higher and IL-17 lower in AD than HC. Among all miRNAs examined, AD showed downregulation of miR-9, miR-21, miR29-b, miR-122, and miR-132 compared to controls. MiR-122 positively and significantly correlated with some inflammatory molecules (GM-CSF, INF-α2, IL-1α, IL-8, and MIP-1β) as well as with α-tocopherol even after correction for age and gender. A final binary logistic regression analysis showed that α-tocopherol serum levels were associated with a higher AD probability and partially mediated by miR-122. Our results suggest an interplay between α-tocopherol, inflammatory molecules, and microRNAs in AD, where miR-122 may be a good candidate as modulating factor.

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Section: Discussionmentioning

confidence: 99%

miRNAs and Alzheimer’s Disease: Exploring the Role of Inflammation and Vitamin E in an Old-Age Population

et al. 2023

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“…The copyright holder for this preprint this version posted June 17, 2024. ; https://doi.org/10.1101/2024.06.14.599092 doi: bioRxiv preprint pathology. 56 These results suggested that stress response-related modules with HSPA5 in GPMNB+ activated microglia are drivers of the pathogenesis of AD and function by moderating Aβ-tau interactions in early-stage AD. These factors are potential biomarkers for early-stage AD.…”

Section: Discussionmentioning

confidence: 83%

“…This finding aligns with those of previous reports indicating that GPNMB expression is correlated with disease pathology. 56 These results suggested that stress response-related modules with HSPA5 in GPMNB+ activated microglia are drivers of the pathogenesis of AD and function by moderating Aβ-tau interactions in early-stage AD. These factors are potential biomarkers for early-stage AD.…”

Section: Discussionmentioning

confidence: 83%

GPNMB+ microglia moderate the amyloid beta-tau interaction in early Alzheimer’s disease

Kitani,

Matsui

2024

Preprint

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SummaryAlthough interactions between amyloid-beta (Aβ) and tau proteins have been implicated in Alzheimer’s disease (AD), the detailed mechanisms by which these interactions contribute to disease progression remain unclear. In this study, we evaluated proteomics and protein–protein interaction data using BIONC, a deep learning-based network integration method to investigate factors moderating the effects of the Aβ-tau interaction in mild cognitive impairment and early-stage AD. Our results suggested that astrocytes and GPNMB+ microglia moderate the Aβ-tau interaction. Based on linear regression with histopathological and gene expression data, GFAP and IBA1 levels andGPNMBgene expression positively contributed to the interaction of tau with Aβ in non-dementia cases, replicating the results of the network analysis. These findings indicate that GPNMB+ microglia moderate the Aβ-tau interaction in early AD and therefore are a novel therapeutic target.Graphical Abstract

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“…Levels of TREM1, another microglial transmembrane protein, were also shown to increase in AD dementia compared with cognitively unimpaired controls and those with mild cognitive impairment (MCI) [14]. In addition, multiple interleukins (ILs) in CSF were associated with Aβ and tau pathology, as well as cognitive decline [15][16][17][18][19][20]. Similarly, several CSF markers of cerebrovascular integrity, such as sPDGFRB (soluble platelet-derived growth factor receptor β), ICAM1, VCAM1, and VEGFs, synaptic markers such as NPTX and NRGN, have been linked to AD and cognitive decline [18,[21][22][23][24][25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Multi-analyte proteomic analysis identifies blood-based neuroinflammation, cerebrovascular and synaptic biomarkers in preclinical Alzheimer’s disease

Zeng,

Lafferty,

Sehrawat

et al. 2024

Preprint

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BackgroundBlood-based biomarkers are gaining grounds for Alzheimer’s disease (AD) detection. However, two key obstacles need to be addressed: the lack of methods for multi-analyte assessments and the need for markers of neuroinflammation, vascular, and synaptic dysfunction. Here, we evaluated a novel multi-analyte biomarker platform, NULISAseq CNS disease panel, a multiplex NUcleic acid-linked Immuno-Sandwich Assay (NULISA) targeting ∼120 analytes, including classical AD biomarkers and key proteins defining various disease hallmarks.MethodsThe NULISAseq panel was applied to 176 plasma samples from the MYHAT-NI cohort of cognitively normal participants from an economically underserved region in Western Pennsylvania. Classical AD biomarkers, including p-tau181, p-tau217, p-tau231, GFAP, NEFL, Aβ40, and Aβ42, were also measured using Single Molecule Array (Simoa). Amyloid pathology, tau pathology, and neurodegeneration were evaluated with [11C] PiB PET, [18F]AV-1451 PET, and MRI, respectively. Linear mixed models were used to examine cross-sectional and Wilcoxon rank sum tests for longitudinal associations between NULISA biomarkers and AD pathologies. Spearman correlations were used to compare NULISA and Simoa.ResultsNULISA concurrently measured 116 plasma biomarkers with good technical performance, and good correlation with Simoa measures. Cross-sectionally, p-tau217 was the top hit to identify Aβ pathology, with age, sex, andAPOEgenotype-adjusted AUC of 0.930 (95%CI: 0.878-0.983). Fourteen markers were significantly decreased in Aβ-PET+ participants, including TIMP3, which regulates brain Aβ production, the neurotrophic factor BDNF, the energy metabolism marker MDH1, and several cytokines. Longitudinally, FGF2, IL4, and IL9 exhibited Aβ PET-dependent yearly increases in Aβ-PET+ participants. Markers with tau PET-dependent longitudinal changes included the microglial activation marker CHIT1, the reactive astrogliosis marker CHI3L1, the synaptic protein NPTX1, and the cerebrovascular markers PGF, PDGFRB, and VEFGA; all previously linked to AD but only reliably measured in cerebrospinal fluid. SQSTM1, the autophagosome cargo protein, exhibited a significant association with neurodegeneration status after adjusting age, sex, andAPOEε4 genotype.ConclusionsTogether, our results demonstrate the feasibility and potential of immunoassay-based multiplexing to provide a comprehensive view of AD-associated proteomic changes. Further validation of the identified inflammation, synaptic, and vascular markers will be important for establishing disease state markers in asymptomatic AD.

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The cerebrospinal fluid interleukin 8 (IL‐8) concentration in Alzheimer’s disease (AD)

Cited by 6 publications

References 0 publications

miRNAs and Alzheimer’s Disease: Exploring the Role of Inflammation and Vitamin E in an Old-Age Population

miRNAs and Alzheimer’s Disease: Exploring the Role of Inflammation and Vitamin E in an Old-Age Population

GPNMB+ microglia moderate the amyloid beta-tau interaction in early Alzheimer’s disease

Multi-analyte proteomic analysis identifies blood-based neuroinflammation, cerebrovascular and synaptic biomarkers in preclinical Alzheimer’s disease

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