Association between serum NPTX2 and cognitive function in patients with vascular dementia

Shao, Keke; Shan, Shiqin; Ru, Wenwen; Ma, Cuihua

doi:10.1002/brb3.1779

Cited by 22 publications

(18 citation statements)

References 27 publications

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“…NPTX2 belongs to the neuronal pentraxin family, whose promoter was frequently highly methylated in many solid tumors ( Park et al, 2007 ; Shukla et al, 2013 ; Rasmussen et al, 2017 ; Alholle et al, 2013 ; Xu et al, 2021a ). Decreased NPTX2 level has been reported to be associated with diverse neurological diseases, including Alzheimer’s disease, anxiety, vascular dementia, Parkinson’s disease and ischemia ( Moran et al, 2008 ; Chang et al, 2018 ; Cai et al, 2019 ; Shao et al, 2020 ; Libiger et al, 2021 ). RTN1, the first identified member of the RTNs family, is predominantly expressed by neurons.…”

Section: Discussionmentioning

confidence: 99%

Promoter Hypomethylation of TGFBR3 as a Risk Factor of Alzheimer’s Disease: An Integrated Epigenomic-Transcriptomic Analysis

Song

Yang

2022

Front. Cell Dev. Biol.

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Alzheimer’s disease (AD) is characterized by the abnormal deposition of amyloid-β (Aβ) plaques and tau tangles in the brain and accompanied with cognitive impairment. However, the fundamental cause of this disease remains elusive. To elucidate the molecular processes related to AD, we carried out an integrated analysis utilizing gene expression microarrays (GSE36980 and GSE5281) and DNA methylation microarray (GSE66351) in temporal cortex of AD patients from the Gene Expression Omnibus (GEO) database. We totally discovered 409 aberrantly methylated and differentially expressed genes. These dysregulated genes were significantly enriched in biological processes including cell part morphogenesis, chemical synaptic transmission and regulation of Aβ formation. Through convergent functional genomic (CFG) analysis, expression cross-validation and clinicopathological correlation analysis, higher TGFBR3 level was observed in AD and positively correlated with Aβ accumulation. Meanwhile, the promoter methylation level of TGFBR3 was reduced in AD and negatively associated with Aβ level and advanced Braak stage. Mechanically, TGFBR3 might promote Aβ production by enhancing β- and γ-secretase activities. Further investigation revealed that TGFBR3 may exert its functions via Synaptic vesicle cycle, Calcium signaling pathway and MAPK signal pathway by regulating hub genes GNB1, GNG3, CDC5L, DYNC1H1 and FBXW7. Overall, our findings highlighted TGFBR3 as an AD risk gene and might be used as a diagnostic biomarker and therapeutic target for AD treatment.

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Section: Discussionmentioning

confidence: 99%

Promoter Hypomethylation of TGFBR3 as a Risk Factor of Alzheimer’s Disease: An Integrated Epigenomic-Transcriptomic Analysis

Song

Yang

2022

Front. Cell Dev. Biol.

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“…Recently, low CSF neuronal pentraxin-2 (NPTX2) concentration was reported in adults with DS. NPTX2, is a promising biofluid surrogate marker of inhibitory circuit dysfunction and cognitive decline in different dementias [48][49][50]. In DS, NPTX2 correlates with cortical atrophy and reduced glucose metabolism [51], but levels did not correlate with measures of cognitive decline.…”

Section: Csf Biomarkersmentioning

confidence: 99%

Blood Biomarkers for Alzheimer’s Disease in Down Syndrome

Montoliu‐Gaya

Strydom

Blennow

et al. 2021

JCM

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Epidemiological evidence suggests that by the age of 40 years, all individuals with Down syndrome (DS) have Alzheimer’s disease (AD) neuropathology. Clinical diagnosis of dementia by cognitive assessment is complex in these patients due to the pre-existing and varying intellectual disability, which may mask subtle declines in cognitive functioning. Cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers, although accurate, are expensive, invasive, and particularly challenging in such a vulnerable population. The advances in ultra-sensitive detection methods have highlighted blood biomarkers as a valuable and realistic tool for AD diagnosis. Studies with DS patients have proven the potential blood-based biomarkers for sporadic AD (amyloid-β, tau, phosphorylated tau, and neurofilament light chain) to be useful in this population. In addition, biomarkers related to other pathologies that could aggravate dementia progression—such as inflammatory dysregulation, energetic imbalance, or oxidative stress—have been explored. This review serves to provide a brief overview of the main findings from the limited neuroimaging and CSF studies, outline the current state of blood biomarkers to diagnose AD in patients with DS, discuss possible past limitations of the research, and suggest considerations for developing and validating blood-based biomarkers in the future.

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“…Neuronal Pentraxin-2 (NPTX2), a protein involved in inhibitory circuit dysfunction (10) is a promising bio uid surrogate marker of inhibitory circuit dysfunction and cognitive decline in sporadic AD (11)(12)(13), vascular dementia (14), genetic frontotemporal dementia (15) and Lewy body dementia (16). We recently reported low CSF NPTX2 concentrations in adults with DS across the AD continuum, which correlated with cortical atrophy and reduced glucose metabolism.…”

Section: Introductionmentioning

confidence: 99%

VAMP-2 Is a Surrogate Cerebrospinal Fluid Marker of Alzheimer-related Cognitive Impairment in Adults With Down Syndrome

Lleó

Carmona‐Iragui

Videla

et al. 2021

Preprint

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Background. There is an urgent need for objective markers of Alzheimer’s disease (AD)-related cognitive impairment in people with Down syndrome (DS) to improve diagnosis, monitor disease progression and assess response to disease-modifying therapies. Previously, GluA4 and Neuronal Pentraxin 2 (NPTX2) showed limited potential as cerebrospinal fluid (CSF) markers of cognitive impairment in adults with DS. Here we compare the CSF profile of a panel of synaptic proteins (Calsyntenin-1, Neuroligin-2, Neurexin-2A, Neurexin-3A, Syntaxin-1B, Thy-1, VAMP-2) to that of NPTX2 and GluA4 in a large cohort of subjects with DS across the preclinical and clinical AD continuum and explore their correlation with cognitive impairment. Methods. We quantified the synaptic panel proteins by selected reaction monitoring in CSF from 20 non-trisomic cognitively normal controls (mean age 44) and 80 adults with DS grouped according to clinical AD diagnosis (asymptomatic, prodromal AD or AD dementia). We used regression analyses to determine CSF changes across the AD continuum and explored correlations with age, global cognitive performance (CAMCOG), episodic memory (modified cued-recall test; mCRT) and CSF AD biomarkers, CSF Aβ42:40 ratio, CSF Aβ1-42 and CSF p-tau. P-values were adjusted for multiple testing. Results. In adults with DS, VAMP-2 was the only synaptic protein to correlate with episodic memory (delayed recall adj.p=.04) and age (adj.p=.0008) and was the best correlate of CSF Aβ42:40 (adj.p=.0001) and CSF p-tau (adj.p<.0001). Compared to controls, mean VAMP-2 levels were lower in asymptomatic adults with DS only (adj.p=.02). CSF levels of Neurexin-3A, Thy-1, Neurexin-2A, Calysntenin-1, Neuroligin-2, GluA4 and Syntaxin-1B all strongly correlated with NPTX2 (p<.0001), which was the only synaptic protein to show reduced CSF levels in DS at all AD stages compared to controls (adj.p<.002). Conclusion. CSF VAMP-2 represents a promising objective surrogate marker of cognitive failure in DS. VAMP-2 also has potential for use in AD clinical trials as a measure of synapse engagement and therapeutic response that does not directly measure the drug target (typically Aβ and tau).

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Association between serum NPTX2 and cognitive function in patients with vascular dementia

Cited by 22 publications

References 27 publications

Promoter Hypomethylation of TGFBR3 as a Risk Factor of Alzheimer’s Disease: An Integrated Epigenomic-Transcriptomic Analysis

Promoter Hypomethylation of TGFBR3 as a Risk Factor of Alzheimer’s Disease: An Integrated Epigenomic-Transcriptomic Analysis

Blood Biomarkers for Alzheimer’s Disease in Down Syndrome

VAMP-2 Is a Surrogate Cerebrospinal Fluid Marker of Alzheimer-related Cognitive Impairment in Adults With Down Syndrome

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