Immunogenomics Parameters for Patient Stratification in Alzheimer’s Disease DOI
Taha I. Huda, Michael J. Diaz, Etienne C. Gozlan

et al.

Journal of Alzheimer s Disease, Journal Year: 2022, Volume and Issue: 88(2), P. 619 - 629

Published: June 3, 2022

Despite the fact that only modest adaptive immune system related approaches to treating Alzheimer's disease (AD) are available, an immunogenomics approach study of AD has not yet substantially advanced.Thus, we sought better understand receptor chemical features in setting.We characterized T-cell alpha (TRA) complementarity determining region-3 (CDR3) physicochemical and identified TRA CDR3 homology groups, represented by recombination reads extracted from 2,665 AD-related, blood- brain-derived exome files.We found a higher isoelectric value for brain CDR3s was associated with (clinically worse) Braak stage number particular representing bloodborne CDR3s, were or lower stages. Lastly, greater both tau, based on recently described CDR3-candidate antigen scoring process (https://adaptivematch.com), stages.Overall, data reported here raise questions (a) whether progression is facilitated response tau; (b) assessment such anti-tau could potentially serve as basis related, risk stratification?

Language: Английский

Virus exposure and neurodegenerative disease risk across national biobanks DOI Creative Commons
Kristin Levine, Hampton L. Leonard, Cornelis Blauwendraat

et al.

Neuron, Journal Year: 2023, Volume and Issue: 111(7), P. 1086 - 1093.e2

Published: Jan. 19, 2023

Language: Английский

Citations

211
Expression of Immune Related Genes and Possible Regulatory Mechanisms in Alzheimer’s Disease DOI Creative Commons
Yanjun Lu, Ke Li, Yu Hu

et al.

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Nov. 5, 2021

Immune infiltration of peripheral natural killer (NK) cells in the brain has been observed Alzheimer’s disease (AD). Immunity-related genes (IRGs) play an essential role immune infiltration; however, expression IRGs and possible regulatory mechanisms involved AD remain unclear. The blood mononuclear (PBMCs) single-cell RNA (scRNA) sequencing data from patients with were analyzed PBMCs obtained ImmPort database screened for cluster marker genes. IRG activity was calculated using AUCell package. A bulk dataset tissues to explore common between brain. Relevant transcription factors (TFs) identified Human TFDB database. protein-protein interaction network key TFs generated STRING Eight clusters identified, including memory CD4 T, NKT, NK, B, DC, CD8 T cells, platelets. NK significantly decreased AD, while increased. DC exhibited highest activity. GO KEGG analyses scRNA showed that DEGs focused on response. Seventy found both Seventeen associated expression, PPI indicated STAT3, IRF1, REL hub TFs. In conclusion, we propose may infiltrate contribute neuroinflammatory changes through bioinformatic analysis data. Moreover, STAT3 be transcriptional regulation cells.

Language: Английский

Citations

65
The gut microbiome and Alzheimer’s disease: Complex and bidirectional interactions DOI Creative Commons
Rawan Tarawneh,

Elena Penhos

Neuroscience & Biobehavioral Reviews, Journal Year: 2022, Volume and Issue: 141, P. 104814 - 104814

Published: Aug. 4, 2022

Language: Английский

Citations

50
Neuroimmune contributions to Alzheimer’s disease: a focus on human data DOI Open Access
Verena Haage, Philip L. De Jager

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 27(8), P. 3164 - 3181

Published: June 6, 2022

Language: Английский

Citations

45
Associations of blood cell indices and anemia with risk of incident dementia: A prospective cohort study of 313,448 participants DOI

Yi‐Xuan Qiang,

Yue‐Ting Deng,

Ya‐Ru Zhang

et al.

Alzheimer s & Dementia, Journal Year: 2023, Volume and Issue: 19(9), P. 3965 - 3976

Published: April 26, 2023

Low hemoglobin and anemia are associated with cognitive impairment Alzheimer's disease (AD). However, the associations of other blood cell indices incident dementia risk underlined mechanisms unknown.

Language: Английский

Citations

31
Neutrophils as a potential therapeutic target in Alzheimer’s disease DOI Creative Commons
Michelle L. Aries, Tiffany Hensley‐McBain

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

Published: March 3, 2023

Alzheimer’s disease (AD) is the leading cause of dementia in United States. Sporadic or late-onset AD remains incompletely understood, with age as current greatest risk factor. Inflammation general and neutrophils, a potent mediator inflammation, have been shown to exacerbate associated dementia. This review explores latest research on neutrophils mouse models human cohort studies discusses gaps needs for future studies. neutrophil chemotactic migration towards amyloid beta plaques brain. Capillary blood flow stalling decreases perfusion brain regions demonstrated that anti-Ly6G antibodies lead decrease capillary memory improvement. Several recent transcriptomic tissue from persons an upregulation neutrophil-related genes, involvement adhesion, barrier breaching, myeloperoxidase release, propensity extracellular trap release AD. Neutrophil-derived inflammation regulation are potential novel therapeutic target progression. Future should further investigate functionality In addition, other aspects may impact including microbiome APOE4 allele be studied.

Language: Английский

Citations

30
N-acetylneuraminic acid links immune exhaustion and accelerated memory deficit in diet-induced obese Alzheimer’s disease mouse model DOI Creative Commons
Stefano Suzzi, Tommaso Croese,

Adi Ravid

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 9, 2023

Abstract Systemic immunity supports lifelong brain function. Obesity posits a chronic burden on systemic immunity. Independently, obesity was shown as risk factor for Alzheimer’s disease (AD). Here we show that high-fat obesogenic diet accelerated recognition-memory impairment in an AD mouse model (5xFAD). In obese 5xFAD mice, hippocampal cells displayed only minor diet-related transcriptional changes, whereas the splenic immune landscape exhibited aging-like CD4 + T-cell deregulation. Following plasma metabolite profiling, identified free N -acetylneuraminic acid (NANA), predominant sialic acid, linking to increased immune-suppressive mice. Single-nucleus RNA-sequencing revealed visceral adipose macrophages potential source of NANA. vitro, NANA reduced proliferation, tested both and human. vivo, administration standard diet-fed mice recapitulated effects T We suggest accelerates manifestation via exhaustion.

Language: Английский

Citations

26
Overlapping Neuroimmune Mechanisms and Therapeutic Targets in Neurodegenerative Disorders DOI Creative Commons
Fabiola De Marchi, Ivana Munitić,

Lea Vidatic

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(10), P. 2793 - 2793

Published: Oct. 14, 2023

Many potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases, such as Alzheimer's (AD) disease, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), well a seemingly distinct Niemann-Pick type C with primarily juvenile onset. This strongly argues for an overlap pathogenic mechanisms. The commonly researched include various cell subsets, microglia, peripheral macrophages, regulatory T cells (Tregs); the complement system; other soluble factors. In this review, we compare these diseases from clinical point of view highlight common pathways mechanisms protein aggregation, neurodegeneration, and/or neuroinflammation that could potentially lead to shared treatment strategies overlapping dysfunctions diseases. These approaches but not limited immunisation, cascade blockade, microbiome regulation, inhibition signal transduction, Treg boosting, stem transplantation.

Language: Английский

Citations

26
Systemic Inflammation in Asthma: What Are the Risks and Impacts Outside the Airway? DOI Creative Commons
Matthew C. Tattersall, Nizar N. Jarjour, Paula Busse

et al.

The Journal of Allergy and Clinical Immunology In Practice, Journal Year: 2024, Volume and Issue: 12(4), P. 849 - 862

Published: Feb. 12, 2024

Language: Английский

Citations

15
Immunophenotypes in psychosis: is it a premature inflamm-aging disorder? DOI Creative Commons
Song Chen, Yunlong Tan, Li Tian

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(9), P. 2834 - 2848

Published: March 26, 2024

Immunopsychiatric field has rapidly accumulated evidence demonstrating the involvement of both innate and adaptive immune components in psychotic disorders such as schizophrenia. Nevertheless, researchers are facing dilemmas discrepant findings immunophenotypes outside inside brains patients, discovered by recent meta-analyses. These discrepancies make interpretations interrogations on their roles psychosis remain vague even controversial, regarding whether certain cells more activated or less so, they causal consequential, beneficial harmful for psychosis. Addressing these issues is not at all trivial, either brain an enormously heterogeneous plastic cell population, falling into a vast range lineages subgroups, functioning differently malleably context-dependent manners. This review aims to overview currently known patients with psychosis, provocatively suggest premature "burnout" inflamm-aging initiated since organ development potential primary mechanism behind pathogenesis disorders.

Language: Английский

Citations

9