THE TRIGGERING RECEPTOR EXPRESSED ON MYELOID CELLS-2 (TREM-2) AS EXPRESSION OF THE RELATIONSHIP BETWEEN MICROGLIA AND ALZHEIMER’S DISEASE: A NOVEL MARKER FOR A PROMISING PATHWAY TO EXPLORE

2018 ◽  
pp. 1-3
Author(s):  
C. Gussago ◽  
M. Casati ◽  
E. Ferri ◽  
B. Arosio
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Variants ◽  
Neurodegenerative Disorder ◽  
Myeloid Cells ◽  
Cell Surface Receptor ◽  
Surface Receptor ◽  
A Cell ◽  
The Relationship ◽  
Common Neurodegenerative Disorder

Alzheimer’s disease (AD) is a common neurodegenerative disorder, strongly related with age. It has been reported that genetic variants of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2), a cell-surface receptor expressed in microglial cells, greatly increase the risk of AD, thus suggesting an involvement of the microglia in the AD pathogenesis. The aim of this report is to provide an overview of the TREM2 and of its possible implication in the pathogenesis of AD.

The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor

Nature ◽  
1987 ◽  
Vol 325 (6106) ◽  
pp. 733-736 ◽  
Author(s):  
Jie Kang ◽  
Hans-Georg Lemaire ◽  
Axel Unterbeck ◽  
J. Michael Salbaum ◽  
Colin L. Masters ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Surface ◽  
Cell Surface Receptor ◽  
Surface Receptor ◽  
A Cell

scholarly journals A combined miRNA–piRNA signature to detect Alzheimer’s disease

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Gaurav Jain ◽  
Anne Stuendl ◽  
Pooja Rao ◽  
Tea Berulava ◽  
Tonatiuh Pena Centeno ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Noncoding Rna ◽  
Clinical Symptoms ◽  
Neurodegenerative Disorder ◽  
Replication Cohort ◽  
Small Noncoding Rna ◽  
Human Cerebrospinal Fluid ◽  
Generation Sequencing ◽  
Common Neurodegenerative Disorder

Abstract Alzheimer’s disease (AD) is the most common neurodegenerative disorder causing huge emotional and economic burden to our societies. An effective therapy has not been implicated yet, which is in part also due to the fact that pathological changes occur years before clinical symptoms manifest. Thus, there is a great need for the development of a translatable biomarker. Recent evidence highlights microRNAs as candidate biomarkers. In this study, we use next-generation sequencing to study the small noncoding RNAome (sncRNAome) in exosomes derived from human cerebrospinal fluid (CSF). We show that the sncRNAome from CSF-derived exosomes is dominated not only by microRNAs (miRNAs) but also by PIWI-interacting RNAs (piRNAs). We define a combined signature consisting of three miRNAs and three piRNAs that are suitable to detect AD with an AUC of 0.83 in a replication cohort and furthermore predict the conversion of mild–cognitive impaired (MCI) patients to AD dementia with an AUC of 0.86 for the piRNA signature. When combining the smallRNA signature with pTau and Aβ 42/40 ratio the AUC reaches 0.98. Our study reports a novel exosomal small noncoding RNA signature to detect AD pathology and provides the first evidence that in addition to miRNAs, piRNAs should also be considered as a candidate biomarker for AD.

scholarly journals Endosomal Trafficking in Alzheimer's Disease, Parkinson's Disease, and Neuronal Ceroid Lipofuscinosis

2020 ◽  
Vol 40 (19) ◽  
Author(s):  
Yasir H. Qureshi ◽  
Penelope Baez ◽  
Christiane Reitz
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Endosomal Trafficking ◽  
Lysosomal Storage ◽  
Ceroid Lipofuscinosis ◽  
Common Neurodegenerative Disorder

ABSTRACT Neuronal ceroid lipofuscinosis (NCL) is one of the most prevalent neurodegenerative disorders of early life, Parkinson’s disease (PD) is the most common neurodegenerative disorder of midlife, while Alzheimer’s disease (AD) is the most common neurodegenerative disorder of late life. While they are phenotypically distinct, recent studies suggest that they share a biological pathway, retromer-dependent endosomal trafficking. A retromer is a multimodular protein assembly critical for sorting and trafficking cargo out of the endosome. As a lysosomal storage disease, all 13 of NCL’s causative genes affect endolysosomal function, and at least four have been directly linked to retromer. PD has several known causative genes, with one directly linked to retromer and others causing endolysosomal dysfunction. AD has over 25 causative genes/risk factors, with several of them linked to retromer or endosomal trafficking dysfunction. In this article, we summarize the emerging evidence on the association of genes causing NCL with retromer function and endosomal trafficking, review the recent evidence linking NCL genes to AD, and discuss how NCL, AD, and PD converge on a shared molecular pathway. We also discuss this pathway’s role in microglia and neurons, cell populations which are critical to proper brain homeostasis and whose dysfunction plays a key role in neurodegeneration.

scholarly journals The Triggering Receptor Expressed on Myeloid Cells 2: “TREM-ming” the Inflammatory Component Associated with Alzheimer's Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Troy T. Rohn
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangles ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Senile Plaques ◽  
Myeloid Cells ◽  
Disease Process ◽  
Age Related

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by a progressive loss of memory and cognitive skills. Although much attention has been devoted concerning the contribution of the microscopic lesions, senile plaques, and neurofibrillary tangles to the disease process, inflammation has long been suspected to play a major role in the etiology of AD. Recently, a novel variant in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) has been identified that has refocused the spotlight back onto inflammation as a major contributing factor in AD. Variants in TREM2 triple one's risk of developing late-onset AD. TREM2 is expressed on microglial cells, the resident macrophages in the CNS, and functions to stimulate phagocytosis on one hand and to suppress cytokine production and inflammation on the other hand. The purpose of this paper is to discuss these recent developments including the potential role that TREM2 normally plays and how loss of function may contribute to AD pathogenesis by enhancing oxidative stress and inflammation within the CNS. In this context, an overview of the pathways linking beta-amyloid, neurofibrillary tangles (NFTs), oxidative stress, and inflammation will be discussed.

Insights from Drosophila models of Alzheimer's disease

2010 ◽  
Vol 38 (4) ◽  
pp. 988-992 ◽  
Author(s):  
Catherine M. Cowan ◽  
David Shepherd ◽  
Amritpal Mudher
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Protein Tau ◽  
Neurodegenerative Process ◽  
Abnormal Hyperphosphorylation ◽  
Ad Alzheimer’S Disease ◽  
The Relationship ◽  
Shed Light ◽  
Drosophila Models

AD (Alzheimer's disease) is a neurodegenerative disorder characterized by the abnormal hyperphosphorylation and aggregation of the microtubule-associated protein tau and the misfolding and deposition of Aβ peptide. The mechanisms by which tau and Aβ become abnormal is not clearly understood, neither is it known what role either protein plays in the neurodegenerative process underlying AD. We have modelled aspects of AD in Drosophila melanogaster to shed light on these processes and to further our understanding of the relationship between tau and amyloid in this disease.

scholarly journals Elevated Oral and Systemic Levels of Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) in Periodontitis

2012 ◽  
Vol 92 (2) ◽  
pp. 161-165 ◽  
Author(s):  
N. Bostanci ◽  
V.Ö. Öztürk ◽  
G. Emingil ◽  
G.N. Belibasakis
Keyword(s):  
Inflammatory Response ◽  
Cell Surface ◽  
Myeloid Cells ◽  
Aggressive Periodontitis ◽  
Cell Surface Receptor ◽  
Immunoglobulin Superfamily ◽  
Control Group ◽  
Inflammatory Biomarker ◽  
Surface Receptor ◽  
A Cell

The Triggering Receptor Expressed on Myeloid cells 1 (TREM-1) is a cell-surface receptor of the immunoglobulin superfamily, involved in the propagation of the inflammatory response to bacterial challenge. Soluble (s)TREM-1 is released from the cell surface during the course of infection and is a useful inflammatory biomarker in the early diagnosis of systemic sepsis. The hypothesis of this study was that oral and systemic levels of sTREM-1 are elevated in periodontitis. Therefore, the aim was to investigate, by ELISA, the sTREM-1 concentrations in saliva and serum of individuals without periodontitis (control) and persons with chronic or generalized aggressive periodontitis. In saliva, sTREM-1 concentrations were higher in chronic and aggressive periodontitis than in the control group, by 3.3-fold and 5.6-fold, respectively. In serum, these differences were 1.7-fold and 2-fold, respectively. However, there were no significant differences between the two forms of periodontitis, neither in saliva nor in serum. Salivary and serum sTREM-1 levels positively correlated with full-mouth clinical periodontal parameters. In conclusion, the increased oral and systemic levels of sTREM-1 in periodontitis denote a value for this molecule as a biomarker for the disease and may also have implications in the association between periodontal infections and systemic inflammatory response.

Alzheimer's disease: inside, outside, upside down

2001 ◽  
Vol 67 ◽  
pp. 15-22 ◽  
Author(s):  
Shi Du Yan ◽  
Ann M. Schmidt ◽  
David Stern
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Surface ◽  
Advanced Glycation Endproducts ◽  
Amyloid Peptide ◽  
Cell Surface Receptor ◽  
Intracellular Enzyme ◽  
Cellular Targets ◽  
Surface Receptor ◽  
High Concentrations

Neurotoxicity of ϐ-amyloid peptide (Aϐ) in Alzheimer's disease (AD) is usually thought to arise from the nonspecific effects of high concentrations of Aϐ on vulnerable neurons, resulting in membrane destabilization and increasing intracellular calcium concentration. This review advances the hypothesis that at early stages of AD, when Aϐ is present in lower amounts, its ability to perturb the function of cellular targets is mediated by specific cofactors present on the cell surface and intracellularly. Receptor for advanced glycation endproducts (RAGE) is a cell-surface receptor which binds Aϐ and amplifies its effects on cells in the nanomolar range. The intracellular enzyme Aϐ-binding alcohol dehydrogenase (ABAD) is likely to engage nascent Aϐ formed in the endoplasmic reticulum, and to mediate cell stress from this site. The analysis of Aϐ interaction with RAGE and ABAD, as well as other cofactors, provides insight into new mechanisms and, potentially, identifies therapeutic targets relevant to neuronal dysfunction in AD.

scholarly journals Non-motor Symptoms in Parkinson’s Disease

2009 ◽  
Vol 4 (1) ◽  
pp. 25 ◽  
Author(s):  
Angelo Antonini ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Motor Symptoms ◽  
Significant Morbidity ◽  
Non Motor Symptoms ◽  
Common Neurodegenerative Disorder

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease and is responsible for significant morbidity and costs. Non-motor manifestations of PD can be as disabling as the classic motor symptoms. Moreover, medications used to treat PD motor symptoms may have variable effects on these non-motor domains.

scholarly journals The fluid biomarkers of Alzheimer’s disease

2021 ◽  
Vol 7 (1) ◽  
pp. 1-16
Author(s):  
Qinyu Peng ◽  
Zhentao Zhang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Neurodegenerative Disorder ◽  
Future Prospects ◽  
Research Directions ◽  
Disease Modifying Therapies ◽  
Highly Sensitive ◽  
Disease Modifying ◽  
Common Neurodegenerative Disorder

Alzheimer’s disease (AD) is the most common neurodegenerative disorder. However, it still has no available disease‐modifying therapies. Its pathology cascade begins decades before symptomatic presentation. For these reasons, highly sensitive and highly specific fluid biomarkers should be developed for the early diagnosis of AD. In this study, the well‐established and emerging fluid biomarkers of AD are summarized, and recent advances on their role in early diagnosis and progression monitoring as well as their correlations with AD pathology are highlighted. Future prospects and related research directions are also discussed.

scholarly journals Dysfunction of Synaptic Vesicle Endocytosis in Parkinson’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Li Zou ◽  
Ye Tian ◽  
Zhentao Zhang
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Synaptic Vesicle ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Progressive Disorder ◽  
Common Neurodegenerative Disorder

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease. It is a chronic and progressive disorder estimated to affect at least 4 million people worldwide. Although the etiology of PD remains unclear, it has been found that the dysfunction of synaptic vesicle endocytosis (SVE) in neural terminal happens before the loss of dopaminergic neurons. Recently, accumulating evidence reveals that the PD-linked synaptic genes, including DNAJC6, SYNJ1, and SH3GL2, significantly contribute to the disruptions of SVE, which is vital for the pathogenesis of PD. In addition, the proteins encoded by other PD-associated genes such as SNCA, LRRK2, PRKN, and DJ-1 also play key roles in the regulation of SVE. Here we present the facts about SVE-related genes and discussed their potential relevance to the pathogenesis of PD.

Sign in / Sign up

Export Citation Format

Share Document