Molecular Neurodegeneration最新文献

{"title":"Alzheimer’s disease pathogenesis: standing at the crossroad of lipid metabolism and immune response","authors":"Zitong Wang, Ling Zhang, Chuan Qin","doi":"10.1186/s13024-025-00857-6","DOIUrl":"https://doi.org/10.1186/s13024-025-00857-6","url":null,"abstract":"Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by macroscopic features such as cortical atrophy, narrowing of the gyri, widening of the sulci, and enlargement of the ventricles. At the cellular level, the pathological characteristics include the extracellular aggregation of β-amyloid (Aβ) forming senile plaques, and the intracellular accumulation of hyperphosphorylated tau proteins forming neurofibrillary tangles. AD leads to the progressive decline of cognitive, behavioral, and social abilities, with no effective treatment available currently. The pathophysiology of AD is complex, involving mechanisms such as immune dysregulation and lipid metabolism alterations. Immune cells, such as microglia, can identify and clear pathological aggregates like Aβ early in the disease. However, prolonged or excessive activation of immune cells may trigger chronic neuroinflammation, thereby accelerating neuronal damage and the progression of AD. Lipid metabolism plays a critical role in maintaining cell membrane structure and function, regulating the production and clearance of Aβ, and supplying energy to the brain. Disruptions in these processes are closely linked to the pathological progression of AD. The interaction between lipid metabolism and the immune system further exacerbates the disease progression of AD. In this review, we discuss the lipid metabolism and immune response in AD, summarize their intricate interactions, and highlight the complexity of the multifactorial pathogenic cascade, offering insights into new interventions targeting the immune-metabolic axis in AD.","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":"31 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD2AP at the junction of nephropathy and Alzheimer’s disease","authors":"Milene Vandal, Mohsen Janmaleki, Isabel Rea, Colin Gunn, Sotaro Hirai, Jeff Biernaskie, Justin Chun, Grant Gordon, Andrey Shaw, Amir Sanati-Nezhad, Gerald Pfeffer, Frederic Calon, Minh Dang Nguyen","doi":"10.1186/s13024-025-00852-x","DOIUrl":"https://doi.org/10.1186/s13024-025-00852-x","url":null,"abstract":"Polymorphisms in the gene encoding CD2-associated protein (CD2AP) are associated with an increased risk for developing Alzheimer’s disease (AD). Intriguingly, variants in the gene also cause a pattern of kidney injury termed focal segmental glomerulosclerosis. Recent studies have investigated the cell types and mechanisms by which CD2AP gene dosage contributes to the key pathological features of AD. This review summarizes the fundamental roles of CD2AP in mammalian cells and systems, discusses the novel pathogenic mechanisms focused on CD2AP in AD and highlights the necessity of incorporating biological sex in CD2AP research. Finally, the article draws important parallels between kidney and brain physiology based on vascular and molecular organization, links kidney disease to AD, and suggests the existence of a kidney-brain axis in AD centered on CD2AP.","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":"42 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early transcriptional and cellular abnormalities in choroid plexus of a mouse model of Alzheimer’s disease","authors":"Zhong-Jiang Yan, Maosen Ye, Jiexi Li, Deng-Feng Zhang, Yong-Gang Yao","doi":"10.1186/s13024-025-00853-w","DOIUrl":"https://doi.org/10.1186/s13024-025-00853-w","url":null,"abstract":"Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β plaques, tau hyperphosphorylation, and neuroinflammation. The choroid plexus (ChP), serving as the blood-cerebrospinal fluid-brain barrier, plays essential roles in immune response to stress and brain homeostasis. However, the cellular and molecular contributions of the ChP to AD progression remain inadequately understood. To elucidate the molecular abnormalities during the early stages of AD, we acquired single-cell transcription profiling of ChP from APP/PS1 mice with early-stage of Aβ pathology and litter-mate controls. The transcriptional alterations that occurred in each cell type were identified by differentially expressed genes, cell–cell communications and pseudotemporal trajectory analysis. The findings were subsequently validated by a series of in situ and in vitro assays. We constructed a comprehensive atlas of ChP at single-cell resolution and identified six major cell types and immune subclusters in male mice. The majority of dysregulated genes were found in the epithelial cells of APP/PS1 mice in comparison to wild-type (WT) mice, and most of these genes belonged to down-regulated module involved in mitochondrial respirasome assembly, cilium organization, and barrier integrity. The disruption of the epithelial barrier resulted in the downregulation of macrophage migration inhibitory factor (MIF) secretion in APP/PS1 mice, leading to macrophage activation and increased phagocytosis of Aβ. Concurrently, ligands (e.g., APOE) secreted by macrophages and other ChP cells facilitated the entry of lipids into ependymal cells, leading to lipid accumulation and the activation of microglia in the brain parenchyma in APP/PS1 mice compared to WT controls. Taken together, these data profiled early transcriptional and cellular abnormalities of ChP within an AD mouse model, providing novel insights of cerebral vasculature into the pathobiology of AD.","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":"129 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging systemic metabolic dysfunction and Alzheimer’s disease: the liver interface","authors":"Dan Song, Yang Li, Ling-Ling Yang, Ya-Xi Luo, Xiu-Qing Yao","doi":"10.1186/s13024-025-00849-6","DOIUrl":"https://doi.org/10.1186/s13024-025-00849-6","url":null,"abstract":"Alzheimer’s disease (AD) is increasingly recognized as a systemic disorder with a substantial metabolic disorder component, where the liver significantly impacts the brain via the liver-brain axis. Key mechanisms include the liver’s role in clearing peripheral β-amyloid (Aβ), the influence of hepatic enzymes and metabolites on cognitive decline, and the systemic effects of metabolic disorders on AD progression. Hepatokines, liver-secreted proteins including fibroblast growth factor (FGF)-21, selenoprotein P (SELENOP), Fetuin-A, Midbrain astrocyte-derived neurotrophic factor (MANF), apolipoprotein J (ApoJ), sex hormone-binding globulin (SHBG), Adropin and Angiopoietin-like protein 3 (ANGPTL3), could regulate insulin sensitivity, lipid metabolism, oxidative stress, immune responses, and neurotrophic support. These pathways are closely linked to core AD pathologies, including Aβ aggregation, tau hyperphosphorylation, neuroinflammation, oxidative stress and mitochondrial dysfunction. Lifestyle interventions, including exercise and dietary modifications, that regulate hepatokines expression may offer novel preventive and therapeutic strategies for AD. This review synthesizes current knowledge on the liver-brain crosstalk in AD, emphasizing the mechanistic role of liver in bridging metabolic dysfunction with neurodegeneration and underscores the diagnostic and therapeutic potential of hepatokines in addressing AD’s complex pathology.","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":"542 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy against tau fragment diminishes AD pathology, improving synaptic function and cognition","authors":"Jie Xiang, Zhengjiang Qian, Ye Xi, Yanuo Wei, Guangxing Wang, Xia Liu, Zhi-Hao Wang, Zhentao Zhang, Shengxi Wu, Keqiang Ye","doi":"10.1186/s13024-025-00854-9","DOIUrl":"https://doi.org/10.1186/s13024-025-00854-9","url":null,"abstract":"Asparagine endopeptidase (AEP) is implicated in the pathogenesis of Alzheimer’s disease (AD) by cleaving Tau at residue N368, accelerating its hyperphosphorylation and aggregation. The Tau N368/t-Tau ratio in cerebrospinal fluid (CSF) serves as a superior biomarker compared to established biomarkers (p-Tau 181/217) for correlating with tau pathology and synaptic dysfunction in patients with AD, highlighting its diagnostic and therapeutic potential. We evaluated the therapeutic efficacy of a Tau N368-specific antibody in two mouse models: Tau P301S (tauopathy) and 3xTg (AD with Aβ/tau pathology). We conducted chronic intraperitoneal administration of the antibody to evaluate its effects on tau aggregation, synaptic integrity, and cognitive function. Neuropathological changes, synaptic plasticity (through electrophysiology), and behavioral outcomes were analyzed alongside Aβ pathology and neuroinflammation in 3xTg mice. Treatment with the anti-Tau N368 antibody significantly diminished neurofibrillary tangles (NFTs) formed of hyperphosphorylated/truncated Tau in both models. Clearance of Tau restored BDNF/TrkB neurotrophic signaling, improved synaptic plasticity, and alleviated cognitive deficits. In 3xTg mice, this treatment also reduced Aβ deposition and neuroinflammation, resulting in enhanced learning and memory. Notably, the antibody’s effectiveness in alleviating both tau and Aβ pathologies indicates a potential interaction between these pathways. Targeting Tau N368 through immunotherapy alleviates tau-driven neurodegeneration, restores synaptic function, and improves accompanying Aβ pathology in AD models. Our results confirmed that Tau N368 is an exceptional biomarker and a promising therapeutic target, disrupting AD progression by addressing tau aggregation and its downstream effects.","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":"15 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutations in NEK1 cause ciliary dysfunction as a novel pathogenic mechanism in amyotrophic lateral sclerosis","authors":"Min-Young Noh, Seong-il Oh, Young-Eun Kim, Sun Joo Cha, Wonjae Sung, Ki-Wook Oh, Yurim Park, Ji Young Mun, Chang-Seok Ki, Minyeop Nahm, Seung Hyun Kim","doi":"10.1186/s13024-025-00848-7","DOIUrl":"https://doi.org/10.1186/s13024-025-00848-7","url":null,"abstract":"Neuronal primary cilia, vital for signaling and cell-cycle regulation, have been implicated in maintaining neuronal identity. While a link between primary ciliary defects and neurodegenerative diseases is emerging, the precise pathological mechanisms remain unclear. We studied the genetic contribution of NEK1 to ALS pathogenesis by analyzing the exome sequences of 920 Korean patients with ALS. To understand the disease contribution of NEK1 variants in ALS, we performed a series of functional studies using patient fibroblasts focusing on primary cilia and microtubule-related phenotypes. In addition, these findings were validated in iPSC-derived motor neurons (iPSC-MNs). NIMA-related kinase 1 (NEK1), a gene encoding a serine/threonine kinase involved in cell cycle regulation, has been identified as a risk gene for amyotrophic lateral sclerosis (ALS). Here, we report that mutations in NEK1 cause primary ciliary abnormality, cell cycle re-entry, and disrupted tubulin acetylation in ALS. We analyzed the whole-exome sequences of 920 Korean patients with sporadic ALS and identified 16 NEK1 variants in 23 patients. We found that two novel variants, p.E853Rfs*9 and p.M1?, reduced NEK1 expression, resulting in loss-of-function (LOF) and one synonymous splicing variant (p.Q132=) exhibited an aberrant isoform lacking exon 5. All three NEK1 variants exhibited abnormal primary ciliary structure, impaired sonic hedgehog signaling, and altered cell-cycle progression. Furthermore, the ALS-linked variants induced intracellular calcium overload followed by Aurora kinase A (AurA)-histone deacetylase (HDAC)6 activation, resulting in ciliary disassembly. These defects were restored by treatment with the intracellular Ca2+ chelator, BAPTA. We also found that NEK1 variants cause decreased α-tubulin acetylation, mitochondrial alteration, and impaired DNA damage response (DDR). Notably, drug treatment to inhibit HDAC6 restored the NEK1-dependent deficits in patient fibroblasts. And, we confirmed that data found in patient fibroblasts were reproduced in iPSC-MNs model. Our results suggest that NEK1 contributes to ALS pathogenesis through the LOF mechanism, and HDAC6 inhibition provides an attractive therapeutic strategy for NEK1 variants associated ALS treatment.","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":"18 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network analysis of the cerebrospinal fluid proteome reveals shared and unique differences between sporadic and familial forms of amyotrophic lateral sclerosis","authors":"Adam N. Trautwig, Edward J. Fox, Eric B. Dammer, Anantharaman Shantaraman, Lingyan Ping, Duc M. Duong, Caroline M. Watson, Fang Wu, Seneshaw Asress, Qi Guo, Allan I. Levey, James J. Lah, Federico Verde, Alberto Doretti, Antonia Ratti, Nicola Ticozzi, Cindy V. Ly, Timothy M. Miller, Mark A. Garret, James D. Berry, Eleanor V. Thomas, Christina N. Fournier, Zachary T. McEachin, Nicholas T. Seyfried, Jonathan D. Glass","doi":"10.1186/s13024-025-00838-9","DOIUrl":"https://doi.org/10.1186/s13024-025-00838-9","url":null,"abstract":"Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease involving loss of motor neurons, typically results in death within 3–5 years of disease onset. Although roughly 10% of cases can be linked to a specific inherited mutation (e.g., C9orf72 hexanucleotide repeat expansion or SOD1 mutation), the cause(s) of most cases are unknown. Consequently, there is a critical need for biomarkers that reflect disease onset and progression across ALS subgroups. We employed tandem mass tag mass spectrometry (TMT-MS) based proteomics on cerebrospinal fluid (CSF) to identify and quantify 2105 proteins from sporadic, C9orf72, and SOD1 ALS patients, asymptomatic C9orf72 expansion carriers, and controls (N = 101). To verify trends in our Emory University cohort we used data-independent acquisition (DIA-MS) on an expanded, four center cohort. This expanded cohort of 259 individuals included 50 sporadic ALS (sALS), 43 C9orf72 ALS, 22 SOD1 ALS, 72 asymptomatic gene carriers (59 C9orf72 and 13 SOD1) and 72 age-matched controls. We identified 2330 proteins and used differential protein abundance and network analyses to determine how protein profiles vary across disease subtypes in ALS CSF. Differential abundance and co-expression network analysis identified proteomic differences between ALS and control, as well as differentially abundant proteins between sporadic, C9orf72 and SOD1 ALS. A panel of proteins differentiated forms of ALS that are indistinguishable in a clinical setting. An additional panel differentiated asymptomatic from symptomatic C9orf72 and SOD1 mutation carriers, marking a pre-symptomatic proteomic signature of genetic forms of ALS. Leveraging this large, multicenter cohort, we validated our ALS CSF network and identified ALS-specific proteins and network modules. This study represents a comprehensive analysis of the CSF proteome across sporadic and genetic causes of ALS that resolves differences among these ALS subgroups and also identifies proteins that distinguish symptomatic from asymptomatic gene carriers. These new data point to varying pathogenic pathways that result in an otherwise clinically indistinguishable disease.","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":"4 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mouse models of Anti-Aβ immunotherapies","authors":"Philip Pikus, R. Scott Turner, G. William Rebeck","doi":"10.1186/s13024-025-00836-x","DOIUrl":"https://doi.org/10.1186/s13024-025-00836-x","url":null,"abstract":"The development of anti-amyloid-beta (Aβ) immunotherapies as the first disease modifying therapy for Alzheimer’s Disease (AD) is a breakthrough of basic research and translational science. Genetically modified mouse models developed to study AD neuropathology and physiology were used for the discovery of Aβ immunotherapies and helped ultimately propel therapies to FDA approval. Nonetheless, the combination of modest efficacy and significant rates of an adverse side effect (amyloid related imaging abnormalities, ARIA), has prompted reverse translational research in these same mouse models to better understand the mechanism of the therapies. This review considers the use of these mouse models in understanding the mechanisms of Aβ clearance, cerebral amyloid angiopathy (CAA), blood brain barrier breakdown, neuroinflammation, and neuronal dysfunction in response to Aβ immunotherapy.","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":"38 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular and molecular mechanisms of pathological tau phosphorylation in traumatic brain injury: implications for chronic traumatic encephalopathy","authors":"Neil Donison, Jacqueline Palik, Kathryn Volkening, Michael J. Strong","doi":"10.1186/s13024-025-00842-z","DOIUrl":"https://doi.org/10.1186/s13024-025-00842-z","url":null,"abstract":"Tau protein plays a critical role in the physiological functioning of the central nervous system by providing structural integrity to the cytoskeletal architecture of neurons and glia through microtubule assembly and stabilization. Under certain pathological conditions, tau is aberrantly phosphorylated and aggregates into neurotoxic fibrillary tangles. The aggregation and cell-to-cell propagation of pathological tau leads to the progressive deterioration of the nervous system. The clinical entity of traumatic brain injury (TBI) ranges from mild to severe and can promote tau aggregation by inducing cellular mechanisms and signalling pathways that increase tau phosphorylation and aggregation. Chronic traumatic encephalopathy (CTE), which is a consequence of repetitive TBI, is a unique tauopathy characterized by pathological tau aggregates located at the depths of the sulci and surrounding blood vessels. The mechanisms leading to increased tau phosphorylation and aggregation in CTE remain to be fully defined but are likely the result of the primary and secondary injury sequelae associated with TBI. The primary injury includes physical and mechanical damage resulting from the head impact and accompanying forces that cause blood–brain barrier disruption and axonal shearing, which primes the central nervous system to be more vulnerable to the subsequent secondary injury mechanisms. A complex interplay of neuroinflammation, oxidative stress, excitotoxicity, and mitochondrial dysfunction activate kinase and cell death pathways, increasing tau phosphorylation, aggregation and neurodegeneration. In this review, we explore the most recent insights into the mechanisms of tau phosphorylation associated with TBI and propose how multiple cellular pathways converge on tau phosphorylation, which may contribute to CTE progression. ","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":"36 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence suggesting that microglia make amyloid from neuronally expressed APP: a hypothesis","authors":"John Hardy, Patrick Lewis","doi":"10.1186/s13024-025-00847-8","DOIUrl":"https://doi.org/10.1186/s13024-025-00847-8","url":null,"abstract":"While APP is largely neuonally expressed, Aβ amyloid is largely produced by microglia as the clearance mechanisms for damaged membranes becomes overwhelmed.","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":"74 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}