Search results for: Amyloid Precursor Protein (APP) N terminal, Human Antibody
#33608391 
2021/03/03
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Flexible and Accurate Substrate Processing with Distinct Presenilin/γ-Secretases in Human Cortical Neurons.
Mutations in the genes (, ) have been linked to the majority of familial Alzheimer's disease (AD). Although great efforts have been made to investigate pathogenic mutations, which ultimately cause an increase in the toxic form of β-amyloid (Aβ), the intrinsic physiological functions of PS in human neurons remain to be determined. In this study, to investigate the physiological roles of PS in human neurons, we generated conditional knock-out (KO) induced pluripotent stem cells (iPSCs), in which PS1 can be selectively abrogated under Cre transduction with or without additional KO. We showed that iPSC-derived neural progenitor cells (NPCs) do not confer a maintenance ability in the absence of both PS1 and PS2, showing the essential role of PS in Notch signaling. We then generated -null human cortical neurons, where PS1 was intact until full neuronal differentiation occurred. Aβ40 production was reduced exclusively in human /-null neurons along with a concomitant accumulation of amyloid β precursor protein (APP)-C-terminal fragments CTFs, whereas Aβ42 was decreased in neurons devoid of Unlike previous studies in mice, in which APP cleavage is largely attributable to PS1, γ-secretase activity seemed to be comparable between PS1 and PS2. In contrast, cleavage of another substrate, N-cadherin, was impaired only in neurons devoid of Moreover, PS2/γ-secretase exists largely in late endosomes/lysosomes, as measured by specific antibody against the γ-secretase complex, in which Aβ42 species are supposedly produced. Using this novel stem cell-based platform, we assessed important physiological PS1/PS2 functions in mature human neurons, the dysfunction of which could underlie AD pathogenesis.Hirotaka Watanabe, Kent Imaizumi, Tetsuo Cai, Zhi Zhou, Taisuke Tomita, Hideyuki Okano
2706 related Products with: Flexible and Accurate Substrate Processing with Distinct Presenilin/γ-Secretases in Human Cortical Neurons.
100 μg100 μg2ug100 μg100.00 ug100 μgOne 96-Well Strip Micropl4 Arrays/Slide100 μg10 100 μg100.00 ug
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#32787955 2020/08/12
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Amyloid precursor protein glycosylation is altered in the brain of patients with Alzheimer's disease.
The amyloid precursor protein (APP) is a transmembrane glycoprotein that undergoes alternative proteolytic processing. Its processing through the amyloidogenic pathway originates a large sAPPβ ectodomain fragment and the β-amyloid peptide, while non-amyloidogenic processing generates sAPPα and shorter non-fibrillar fragments. Hence, measuring sAPPα and sAPPβ has been proposed as a means to identify imbalances between the amyloidogenic/non-amyloidogenic pathways in the brain of Alzheimer's disease (AD) patients. However, to date, no consistent changes in these proteolytic fragments have been identified in either the brain or cerebrospinal fluid of AD individuals.Claudia P Boix, Inmaculada Lopez-Font, Inmaculada Cuchillo-Ibañez, Javier Sáez-Valero
2112 related Products with: Amyloid precursor protein glycosylation is altered in the brain of patients with Alzheimer's disease.
96 tests96 tests96 tests96 tests 100ul100μg5010100 100ul10
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#32399180 2019/07/29
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Validation of a commercial antibody to detect endogenous human nicastrin by immunoblot.
Nicastrin (NCSTN) is a transmembrane glycoprotein that is part of the gamma-secretase complex. Gamma-secretase is a protease complex that cleaves type-I single-pass transmembrane proteins. There are many potential substrates for this complex, including NOTCH receptors and amyloid precursor proteins (APP). There are a number of commercial antibodies to nicastrin, but they do not agree on expected peptide size. We confirmed the specificity of a C-terminal binding rabbit anti-human antibody from Sigma-Aldrich (#N1660) using wildtype HEK293 cells and HEK293 cells deleted for nicastrin. The wildtype cells showed a prominent band at approximately 110 kDa. We confirmed this larger than expected sized was due to glycosylation by treating the lysate with peptide-N-glycosidase F (PNGase F), which reduced the band to less than 75 kDa. These data suggest that this polyclonal is specific for nicastrin and can detect endogenous levels of protein.Rosana A Mesa, Elisha D O Roberson
1031 related Products with: Validation of a commercial antibody to detect endogenous human nicastrin by immunoblot.
1 module1 kit 100ul96 tests 100ul96 tests100ug Lyophilized 100ul
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#32039447 //
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Proinflammatory cytokines induce accumulation of glypican-1-derived heparan sulfate and the C-terminal fragment of β-cleaved APP in autophagosomes of dividing neuronal cells.
Proinflammatory cytokines stimulate expression of β-secretase, which increases processing of amyloid precursor protein (APP), ultimately leading to the deposition of amyloid beta (Aβ). The N-terminal domain of β-cleaved APP supports Cu/NO-dependent release of heparan sulfate (HS) from the glypican-1 (Gpc-1) proteoglycan. HS is an inhibitor of β-secretase, thereby constituting a regulatory, negative feedback loop. Here, we have investigated the effect of the proinflammatory cytokines TNF-α, IL-1β and IL-6 on the interplay between APP processing and release of HS from Gpc-1 in neuronal cells. We have used deconvolution immunofluorescence microscopy and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and a panel of monoclonal/polyclonal antibodies recognizing the released HS, the N-terminus of Aβ, Aβ, the C-terminus of APP and the autophagosome marker LC3 as well as the chemical lysosome marker LysoTrackerRed (LTR). We repeatedly found that N2a neuroblastoma cells and human neural stem cells grown in the presence of the cytokines developed large cytoplasmic clusters, which stained positive for HS, the N-terminus of Aβ, Aβ, the C-terminus of APP, LC3 and LTR, indicating accumulation of HS and APP/APP degradation products in enlarged autophagosomes/lysosomes. The SDS-PAGE of immunoisolates obtained from TNF-α-treated N2a cells by using anti-C-terminus of APP revealed the presence of SDS-stable complexes between HS and the C-terminal fragment of β-cleaved APP (βCTF) migrating in the range 10-18 kDa. Clustered accumulation of βCTF disappeared when HS release was prevented and slightly enhanced when HS release was increased. Hence, when proinflammatory cytokines induce increased processing of APP, inhibition of β-secretase by HS is insufficient, which may lead to the impaired autophagosomal degradation.Fang Cheng, Lars-Åke Fransson, Katrin Mani
1325 related Products with: Proinflammatory cytokines induce accumulation of glypican-1-derived heparan sulfate and the C-terminal fragment of β-cleaved APP in autophagosomes of dividing neuronal cells.
5 G 100ul50 ug 100ul100.00 ug100ug Lyophilized0.1ml1.00 flask
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#31834353 //
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Alzheimer-like amyloid and tau alterations associated with cognitive deficit in temporal lobe epilepsy.
Temporal lobe epilepsy represents a major cause of drug-resistant epilepsy. Cognitive impairment is a frequent comorbidity, but the mechanisms are not fully elucidated. We hypothesized that the cognitive impairment in drug-resistant temporal lobe epilepsy could be due to perturbations of amyloid and tau signalling pathways related to activation of stress kinases, similar to those observed in Alzheimer's disease. We examined these pathways, as well as amyloid-β and tau pathologies in the hippocampus and temporal lobe cortex of drug-resistant temporal lobe epilepsy patients who underwent temporal lobe resection (n = 19), in comparison with age- and region-matched samples from neurologically normal autopsy cases (n = 22). Post-mortem temporal cortex samples from Alzheimer's disease patients (n = 9) were used as positive controls to validate many of the neurodegeneration-related antibodies. Western blot and immunohistochemical analysis of tissue from temporal lobe epilepsy cases revealed increased phosphorylation of full-length amyloid precursor protein and its associated neurotoxic cleavage product amyloid-β*56. Pathological phosphorylation of two distinct tau species was also increased in both regions, but increases in amyloid-β1-42 peptide, the main component of amyloid plaques, were restricted to the hippocampus. Furthermore, several major stress kinases involved in the development of Alzheimer's disease pathology were significantly activated in temporal lobe epilepsy brain samples, including the c-Jun N-terminal kinase and the protein kinase R-like endoplasmic reticulum kinase. In temporal lobe epilepsy cases, hippocampal levels of phosphorylated amyloid precursor protein, its pro-amyloidogenic processing enzyme beta-site amyloid precursor protein cleaving enzyme 1, and both total and hyperphosphorylated tau expression, correlated with impaired preoperative executive function. Our study suggests that neurodegenerative and stress-related processes common to those observed in Alzheimer's disease may contribute to cognitive impairment in drug-resistant temporal lobe epilepsy. In particular, we identified several stress pathways that may represent potential novel therapeutic targets.Sarah Gourmaud, Haochang Shou, David J Irwin, Kimberly Sansalone, Leah M Jacobs, Timothy H Lucas, Eric D Marsh, Kathryn A Davis, Frances E Jensen, Delia M Talos
1463 related Products with: Alzheimer-like amyloid and tau alterations associated with cognitive deficit in temporal lobe epilepsy.
96 tests96 tests96 tests96 tests5 mg100 μg50ul (1mg/ml)100 μg
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#30911579 2019/02/27
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Anti-PrP antibody rescues cognition and synapses in transgenic alzheimer mice.
Amyloid-beta oligomers (Aßo) trigger the development of Alzheimer's disease (AD) pathophysiology. Cellular prion protein (PrPC) initiates synaptic damage as a high affinity receptor for Aßo. Here, we evaluated the preclinical therapeutic efficacy of a fully human monoclonal antibody against PrPC. This AZ59 antibody selectively targets the Aβo binding site in the amino-terminal unstructured domain of PrPC to avoid any potential risk of direct toxicity.Timothy O Cox, Erik C Gunther, A Harrison Brody, Marius T Chiasseu, Austin Stoner, Levi M Smith, Laura T Haas, Jayne Hammersley, Gareth Rees, Bhupinder Dosanjh, Maria Groves, Matthew Gardener, Claire Dobson, Tristan Vaughan, Iain Chessell, Andrew Billinton, Stephen M Strittmatter
2022 related Products with: Anti-PrP antibody rescues cognition and synapses in transgenic alzheimer mice.
100ug Lyophilized100ug Lyophilized100ug100ug100ug Lyophilized100ug100ug100ug Lyophilized100ug Lyophilized100ug100ug Lyophilized100ug
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#30817799 2019/02/28
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Human cerebrospinal fluid 6E10-immunoreactive protein species contain amyloid precursor protein fragments.
In a previous study, we reported that levels of two types of protein species-a type of ~55-kDa species and a type of ~15-kDa species-are elevated in the lumbar cerebrospinal fluid (CSF) of cognitively intact elderly individuals who are at risk for Alzheimer's disease (AD). These species are immunoreactive to the monoclonal antibody 6E10, which is directed against amino acids 6-10 of amyloid-β (Aβ), and their levels correlate with levels of total tau and tau phosphorylated at Thr181. In this study, we investigated the molecular composition of these AD-related proteins using immunoprecipitation (IP)/Western blotting coupled with IP/mass spectrometry. We show that canonical Aβ1-40/42 peptides, together with amyloid-β precursor protein (APP) fragments located N-terminally of Aβ, are present in the ~55-kDa, 6E10-immunoreactive species. We demonstrate that APP fragments located N-terminally of Aβ, plus the N-terminal region of Aβ, are present in the ~15-kDa, 6E10-immunoreactive species. These findings add to the catalog of AD-related Aβ/APP species found in CSF and should motivate further study to determine whether these species may serve as biomarkers of disease progression.Marianne K O Grant, Maureen Handoko, Malgorzata Rozga, Gunnar Brinkmalm, Erik Portelius, Kaj Blennow, Karen H Ashe, Kathleen R Zahs, Peng Liu
1813 related Products with: Human cerebrospinal fluid 6E10-immunoreactive protein species contain amyloid precursor protein fragments.
100ul250ul 100ul250ul250ul 100ul 100ul250ul96T 100ul 100ul0.5 mg
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#30409172 2018/11/08
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Decoding the synaptic dysfunction of bioactive human AD brain soluble Aβ to inspire novel therapeutic avenues for Alzheimer's disease.
Pathologic, biochemical and genetic evidence indicates that accumulation and aggregation of amyloid β-proteins (Aβ) is a critical factor in the pathogenesis of Alzheimer's disease (AD). Several therapeutic interventions attempting to lower Aβ have failed to ameliorate cognitive decline in patients with clinical AD significantly, but most such approaches target only one or two facets of Aβ production/clearance/toxicity and do not consider the heterogeneity of human Aβ species. As synaptic dysfunction may be among the earliest deficits in AD, we used hippocampal long-term potentiation (LTP) as a sensitive indicator of the early neurotoxic effects of Aβ species. Here we confirmed prior findings that soluble Aβ oligomers, much more than fibrillar amyloid plaque cores or Aβ monomers, disrupt synaptic function. Interestingly, not all (84%) human AD brain extracts are able to inhibit LTP and the degree of LTP impairment by AD brain extracts does not correlate with Aβ levels detected by standard ELISAs. Bioactive AD brain extracts also induce neurotoxicity in iPSC-derived human neurons. Shorter forms of Aβ (including Aβ, Aβ, Aβ), pre-Aβ APP fragments (- 30 to - 1) and N-terminally extended Aβs (- 30 to + 40) each showed much less synaptotoxicity than longer Aβs (Aβ - Aβ). We found that antibodies which target the N-terminus, not the C-terminus, efficiently rescued Aβ oligomer-impaired LTP and oligomer-facilitated LTD. Our data suggest that preventing soluble Aβ oligomer formation and targeting their N-terminal residues with antibodies could be an attractive combined therapeutic approach.Shaomin Li, Ming Jin, Lei Liu, Yifan Dang, Beth L Ostaszewski, Dennis J Selkoe
2160 related Products with: Decoding the synaptic dysfunction of bioactive human AD brain soluble Aβ to inspire novel therapeutic avenues for Alzheimer's disease.
96 tests96 tests96 tests96 tests96tests20 ug 50 UG10ìg
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#29690919 2018/04/24
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Lack of human-like extracellular sortilin neuropathology in transgenic Alzheimer's disease model mice and macaques.
Alzheimer's disease (AD) is a devastating neurodegenerative disorder bearing multiple pathological hallmarks suggestive of complex cellular/molecular interplay during pathogenesis. Transgenic mice and nonhuman primates are used as disease models for mechanistic and translational research into AD; the extent to which these animal models recapitulate AD-type neuropathology is an issue of importance. Putative C-terminal fragments from sortilin, a member of the vacuolar protein sorting 10 protein (Vps10p) family, have recently been shown to deposit in the neuritic β-amyloid (Aβ) plaques in the human brain.Feng-Qin Zhou, Juan Jiang, Chelsea M Griffith, Peter R Patrylo, Huaibin Cai, Yaping Chu, Xiao-Xin Yan
1036 related Products with: Lack of human-like extracellular sortilin neuropathology in transgenic Alzheimer's disease model mice and macaques.
96 tests96 tests96 tests96 tests100 μg100 μg96 wells (1 kit)10 4 Arrays/Slide96tests4 Membranes/Box
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#29094307 2017/11/01
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Plant-based chimeric HPV-virus-like particles bearing amyloid-β epitopes elicit antibodies able to recognize amyloid plaques in APP-tg mouse and Alzheimer's disease brains.
The main amyloid-beta (Aβ) variants detected in the human brain are full-length Aβ1-40 and Aβ1-42 peptides; however, a significant proportion of AD brain Aβ consists also of N-terminal truncated/modified species. The majority of the previous immunotherapeutic strategies targeted the N-terminal immunodominant epitope of the full-length Aβ; however, most of the pathological N-truncated forms of Aβ lack this critical B cell epitope. Recently, virus-like particles (VLPs), self-assembled structures with highly ordered repetitive patterns on their surface and capable of inducing robust immune responses, were applied as a promising platform for various antigen expressions. In this study, we expressed in plants two chimeric HPV16 L1 capsid proteins obtained by introduction of the β-amyloid 11-28 epitope (Aβ 11-28) into the h4 helix or into the coil regions of the L1 protein. The Aβ 11-28 epitope was chosen because it is present in the full-length Aβ 1-42 as well as in the truncated/modified amyloid peptide species. After expression, we assembled the chimerical L1/Aβ 11-28 into a VLP in which the Aβ 11-28 epitope is exposed at very high density (360 times) on the surface of the VLP. The chimeric VLPs elicited in mice Aβ-specific antibodies binding to β-amyloid plaques in APP-tg mouse and AD brains. Our study is the first to demonstrate a successful production in plants and immunogenic properties in mice of chimeric HPV16 L1 VLPs bearing Aβ epitope that may be of potential relevance for the development of multivalent vaccines for a multifactorial disease such as AD.R Gonzalez-Castro, G Acero Galindo, Y García Salcedo, L Uribe Campero, V Vazquez Perez, M Carrillo-Tripp, G Gevorkian, M A Gomez Lim