Abstract:
:Synaptic neurodegeneration is thought to be an early event initiated by soluble β-amyloid (Aβ) aggregates that closely correlates with cognitive decline in Alzheimer disease (AD). Apolipoprotein ε4 (APOE4) is the most common genetic risk factor for both familial AD (FAD) and sporadic AD; it accelerates Aβ aggregation and selectively impairs glutamate receptor function and synaptic plasticity. However, its molecular mechanisms remain elusive and these synaptic deficits are difficult to monitor. AD- and APOE4-dependent plasma biomarkers have been proposed, but synapse-related plasma biomarkers are lacking. We evaluated neuronal pentraxin 1 (NP1), a potential CNS-derived plasma biomarker of excitatory synaptic pathology. NP1 is preferentially expressed in brain and involved in glutamate receptor internalization. NP1 is secreted presynaptically induced by Aβ oligomers, and implicated in excitatory synaptic and mitochondrial deficits. Levels of NP1 and its fragments were increased in a correlated fashion in both brain and plasma of 7-8 month-old E4FAD mice relative to E3FAD mice. NP1 was also found in exosome preparations and reduced by dietary DHA supplementation. Plasma NP1 was higher in E4FAD+ (APOE4+/+/FAD+/-) relative to E4FAD- (non-carrier; APOE4+/+/FAD-/-) mice, suggesting NP1 is modulated by Aβ expression. Finally, relative to normal elderly, plasma NP1 was also elevated in patients with mild cognitive impairment (MCI) and elevated further in the subset who progressed to early-stage AD. In those patients, there was a trend towards increased NP1 levels in APOE4 carriers relative to non-carriers. These findings indicate that NP1 may represent a potential synapse-derived plasma biomarker relevant to early alterations in excitatory synapses in MCI and early-stage AD.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Ma QL,Teng E,Zuo X,Jones M,Teter B,Zhao EY,Zhu C,Bilousova T,Gylys KH,Apostolova LG,LaDu MJ,Hossain MA,Frautschy SA,Cole GMdoi
10.1016/j.nbd.2018.02.014subject
Has Abstractpub_date
2018-06-01 00:00:00pages
120-128eissn
0969-9961issn
1095-953Xpii
S0969-9961(18)30046-9journal_volume
114pub_type
杂志文章abstract::Neurodegenerative diseases encompass a large group of neurological disorders. Clinical symptoms can include memory loss, cognitive impairment, loss of movement or loss of control of movement, and loss of sensation. Symptoms are typically adult onset (although severe cases can occur in adolescents) and are reflective o...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2010.05.026
更新日期:2010-10-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is characterised by substantial loss of both upper and lower motor neuron function, with sensory and cognitive systems less affected. Though heritable forms of the disease have been described, the vast majority of cases are sporadic with poorly defined underlying pathogenic mechanis...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2012.06.016
更新日期:2012-10-01 00:00:00
abstract::Dietary or pharmacological manipulation of plasma lipids markedly influences amyloid deposition in animal models of Alzheimer's Disease (AD). However, it is not known whether baseline plasma lipids in AD models differ from wild-type littermates throughout the natural history of disease. To address this question, we me...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2006.06.007
更新日期:2006-10-01 00:00:00
abstract::Huntington's disease (HD) and Dentatorubral and pallidoluysian atrophy (DRPLA) are autosomal dominant, neurodegenerative disorders caused by the expansion of polyglutamine tracts in their respective proteins, huntingtin and atrophin-1. We have previously generated mouse models of these disorders, using transgenes expr...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1006/nbdi.2001.0385
更新日期:2001-06-01 00:00:00
abstract::GDAP1 is an outer mitochondrial membrane protein that acts as a regulator of mitochondrial dynamics. Mutations of the GDAP1 gene cause Charcot-Marie-Tooth (CMT) neuropathy. We show that GDAP1 interacts with the vesicle-organelle trafficking proteins RAB6B and caytaxin, which suggests that GDAP1 may participate in the ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.03.010
更新日期:2013-07-01 00:00:00
abstract::We identified a novel spontaneous mutant mouse showing motor symptoms that are similar to those of the dystonia musculorum (dt) mouse. The observations suggested that the mutant mice inherited the mild dt phenotype as an autosomal recessive trait. Linkage analysis showed that the causative gene was located near D1Mit3...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2016.09.016
更新日期:2016-12-01 00:00:00
abstract::Inhibition of mitochondrial axonal trafficking by amyloid beta (Aβ) peptides has been implicated in early pathophysiology of Alzheimer's Disease (AD). Yet, it remains unclear whether the loss of motility inevitably induces the loss of mitochondrial function, and whether restoration of axonal trafficking represents a v...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2018.02.003
更新日期:2018-06-01 00:00:00
abstract::Huntington's disease (HD) is a neurodegenerative disorder involving progressive motor disturbances, cognitive decline, and desynchronized sleep-wake rhythms. Recent studies revealed that restoring normal sleep-wake cycles can improve cognitive function in HD mice, suggesting that some sleep/wake systems remain operati...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2011.02.006
更新日期:2011-06-01 00:00:00
abstract::The motor cortex and subthalamic nucleus (STN) of patients with Parkinson's disease (PD) exhibit abnormally high levels of electrophysiological oscillations in the ~12-35 Hz beta-frequency range. Recent studies have shown that beta is partly carried forward to regulate future motor states in the healthy condition, sug...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2018.05.013
更新日期:2018-09-01 00:00:00
abstract::To decipher the pathway of apoptosis induction downstream to caspase-8 activation by exogenous expression of Hippi, an interactor of huntingtin-interacting protein Hip1, we studied apoptosis in HeLa and Neuro2A cells expressing GFP-tagged Hippi. Nuclear fragmentation, caspase-1, caspase-8, caspase-9/caspase-6 and casp...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.11.003
更新日期:2006-05-01 00:00:00
abstract::The autophagy-lysosomal degradation pathway plays a role in the onset and progression of neurodegenerative diseases. Clinical and genetic studies indicate that mutations of beta-glucocerebrosidase represent genetic risk factors for synucleinopathies, including Parkinson's Disease (PD) and Dementia with Lewy Bodies (DL...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2009.03.002
更新日期:2009-06-01 00:00:00
abstract::Oxidative stress is involved in the pathogenesis of various neurodegenerative disorders, conventional antioxidant strategies have yet been of limited success. We have employed transgenic Caenorhabditis elegans expressing DsRed2 in dopaminergic neurons and CFP pan-neuronally, to characterize in larval and adult animals...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2010.03.019
更新日期:2010-10-01 00:00:00
abstract::Pathological oxygen deprivation inhibits prolyl hydroxylase (PHD) activity and stimulates a protective cellular oxygen-sensing response in part through the stabilization and activation of the Hypoxia Inducible Factor (HIF) 1α transcription factor. The present investigation tested the therapeutic potential of enhanced ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2011.10.020
更新日期:2012-02-01 00:00:00
abstract::Photoreceptor cell death is an irreversible, pathologic event in many blinding retinal diseases including retinitis pigmentosa, age-related macular disease, and retinal detachment. Light exposure can exacerbate a variety of human retinal diseases by increasing the rate of photoreceptor cell death. In the present study...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.08.017
更新日期:2006-03-01 00:00:00
abstract::beta-Amyloid is cytotoxic to neurons in culture by increasing hydrogen peroxide and altering calcium homeostasis. We have evaluated the cytotoxicty of beta-amyloid peptides (betaA(25-35) and betaA(1-40)) and generation of hydrogen peroxide on cortical cultured astrocytes. Twenty-four hours after a single addition of e...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1006/nbdi.2000.0313
更新日期:2000-08-01 00:00:00
abstract::We have explored the molecular mechanism underlying amyloid beta-peptide (Abeta)-mediated cytotoxicity in vitro. Exposure of murine cerebral endothelial cells (CECs) or C6 glioma cells to Abeta25-35 resulted in dose-dependent cell death. Ceramide is a pro-apoptotic lipid mediator. Forced elevation of cellular ceramide...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2004.06.001
更新日期:2004-10-01 00:00:00
abstract::Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an excessive expansion of a CAG trinucleotide repeat in the gene encoding the protein huntingtin, resulting in an elongated stretch of glutamines near the N-terminus of the protein. Here we report the derivation of a collection of ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2011.12.032
更新日期:2012-04-01 00:00:00
abstract::Toll-like receptors (TLRs) are mediators of the innate immune response to exogenous pathogens. They have also been implicated in sterile inflammation associated with systemic injury and non-infectious diseases via binding of endogenous ligands, possibly released by damaged cells. Emerging evidence indicates that some ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2012.12.012
更新日期:2013-06-01 00:00:00
abstract::Alzheimer's disease is widely held to be associated with oxidative stress due, in part, to the membrane action of amyloid beta-peptide (A beta) aggregates. In this study, the involvement of oxidative stress on A beta-induced energy metabolism dysfunction was evaluated on PC12 cells. It was shown that A beta peptides (...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1006/nbdi.1999.0241
更新日期:1999-06-01 00:00:00
abstract::Spinocerebellar ataxia type 3 (SCA3) or Machado-Joseph disease (MJD) belongs to a group of autosomal dominant neurodegenerative diseases, which are caused by the expansion of a polyglutamine repeat in the affected protein, in this case ataxin-3. Ataxin-3 is mainly localized in the cytoplasm; however, one hallmark of S...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2009.07.020
更新日期:2009-11-01 00:00:00
abstract::The interest in the pedunculopontine tegmental nucleus (PPTg), a structure located in the brainstem at the level of the pontomesencephalic junction, has greatly increased in recent years because it is involved in the regulation of physiological functions that fail in Parkinson's disease and because it is a promising t...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2018.03.004
更新日期:2019-08-01 00:00:00
abstract::Giliosis is a hallmark of prion disease. A neurotoxic prion peptide (PrP106-126) induces astrocyte proliferation in the presence of microglia. This peptide also directly enhances microglial proliferation in culture. We have investigated this further to understand the method by which factors released by microglia and P...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1006/nbdi.1998.0169
更新日期:1998-04-01 00:00:00
abstract::Deep brain stimulation for epilepsy has garnered attention from epileptologists due to its well-documented success in treating movement disorders and the low morbidity associated with the implantation of electrodes. Given the large proportion of patients who fail medical therapy and are not candidates for surgical ame...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2009.07.007
更新日期:2010-06-01 00:00:00
abstract::Developing in vivo functional and structural neuroimaging assays in Dyt1 ΔGAG heterozygous knock-in (Dyt1 KI) mice provide insight into the pathophysiology underlying DYT1 dystonia. In the current study, we examined in vivo functional connectivity of large-scale cortical and subcortical networks in Dyt1 KI mice and wi...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2016.07.005
更新日期:2016-11-01 00:00:00
abstract::This article reviews three concepts related to implantable brain computer interface (BCI) devices being designed for human use: neural signal extraction primarily for motor commands, signal insertion to restore sensation, and technological challenges that remain. A significant body of literature has occurred over the ...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2009.12.007
更新日期:2010-06-01 00:00:00
abstract::Huntington disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat. Its length can be used to estimate the time of clinical diagnosis, which is defined by overt motor symptoms. Non-motor symptoms begin before motor onset, and involve changes in hypothalamus-regulated functions such as sleep...
journal_title:Neurobiology of disease
pub_type: 杂志文章,多中心研究
doi:10.1016/j.nbd.2010.07.013
更新日期:2010-12-01 00:00:00
abstract::All tauopathies result in various forms of cognitive decline and neuronal loss. Although in some diseases, tau mutations appear to cause neurodegeneration, the toxic "form" of tau remains elusive. Tau is the major protein found within neurofibrillary tangles (NFTs) and therefore it seemed rational to assume that aggre...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2014.03.002
更新日期:2014-07-01 00:00:00
abstract::The amyloid precursor protein (APP) is a type I transmembrane protein translocated to neuronal terminals, whose function is still unknown. The C-terminus of APP mediates its interaction with cellular adaptor and signaling proteins, some of which signal to the stress-activated protein kinase (SAPK) pathway. Here we sho...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2007.06.017
更新日期:2007-10-01 00:00:00
abstract::The deposition and accumulation of amyloid-beta-peptide (Abeta) in the brain are considered a sine qua non for Alzheimer's disease. The experimental delivery of fibrilized Abeta serves as a cellular model for several facets of the disease including the induction of synaptic dysfunction and apoptosis. c-Abl kinase is i...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2004.06.007
更新日期:2004-11-01 00:00:00
abstract:BACKGROUND:Alzheimer's disease (AD) is the most common neurodegenerative disorder. Depositions of amyloid β peptide (Aβ) and tau protein are among the major pathological hallmarks of AD. Aβ and tau burden follows predictable spatial patterns during the progression of AD. Nevertheless, it remains obscure why certain bra...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2019.104509
更新日期:2019-10-01 00:00:00