Functional Alterations in the Olfactory Neuronal Circuit Occur before Hippocampal Plasticity Deficits in the P301S Mouse Model of Tauopathy: Implications for Early Diagnosis and Translational Research in Alzheimer’s Disease
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Functional Alterations in the Olfactory Neuronal Circuit Occur before Hippocampal Plasticity Deficits in the P301S Mouse Model of Tauopathy: Implications for Early Diagnosis and Translational Research in Alzheimer’s Disease
Alzheimer’s disease (AD) is characterized by loss of neurons and synaptic transmission interruption, eventually causing cognitive deficits. At the beginning of the disease, the olfactory pathways appear to be most sensitive to tauopathy, while most studies have focused on the plasticity of hippocampal circuits.
Functional network connectivity (FC) and long-term potentiation (LTP), regarded as the substrate plasticity of learning and memory, which is longitudinally assessed on a rat model of P301S of tauopathy follow courses (time and location) pathology of progressive neurodegenerative (ie, at 3, 6, and 9 months of age) and their wild-type (WT) littermates. Using in vivo potency local field (LFP) recordings, beginning (at three months) absorbers in activity oscillates gamma and interference in the coupling phase-amplitude theta-gamma (PAC) found in the olfactory bulb (OB) circuitry P301S mice, which was maintained through the entire program of development of pathology. In contrast, activity LFP oscillations and normal PAC index in the entorhinal cortex, hippocampal CA1 and CA3 core.
Field excitatory postsynaptic potential (fEPSP) recording of collateral Shaffer (SC) -CA1 hippocampal LTP strata of the pyramid reveals significantly altered synaptic responses against high frequency stimulation (HFS): at three months of age, there was no significant difference between the genotype was found in the basal synaptic activity , while signs of short-term plasticity deficits revealed by changes in fEPSPs. At the age of six months, a little deviation found in the basal synaptic activity and significant differences were observed in response to the LTP. The change in network oscillations in the level of OB and disruption in the functioning of the SC-CA1 synapses pyramid strongly suggest that the development of tau pathology causing brain areas, disruption of activity-dependent synaptic transmission functional.
These findings indicate a major change early activity of neurons in the OB circuit before hippocampal synaptic plasticity disorders, may involve tauopathy in anomaly FC. Further studies should determine whether they are deficits in the early oscillation OB and FC network is a mechanism that may potentially promote the emergence of hippocampal synaptic disruption during development tauopathy.
Functional Alterations in the Olfactory Neuronal Circuit Occur before Hippocampal Plasticity Deficits in the P301S Mouse Model of Tauopathy: Implications for Early Diagnosis and Translational Research in Alzheimer’s Disease
Use of Biomarkers in ongoing Alzheimer’s Disease Research Protocols
This study aims to describe and discuss the state of the art the use of biomarkers in the ongoing study of disease (AD) Alzheimer’s. A review of 222 ongoing phase 1, 2, 3, and 4 protocols listed in the database clinicaltrials.gov do. All trials (i) subjects enrolled in a clinical disorder and / or diagnosis of preclinical included in the continuum of AD; and (ii) to test the efficacy and / or safety / tolerability of the therapeutic intervention, were analyzed.
The use of biomarkers of amyloid deposition, tau pathology and neurodegeneration among the eligibility criteria and / or the results of the study assessed. Overall, 58.2% of the intervention study was underway on adopting AD biomarker candidates. They largely adopted by studies in the early stages of the drug development process to explore the safety profile of new therapies, and to provide evidence of target engagement and disease-modifying properties.
Description: Human hippocamps tissue lysate was prepared by homogenization using a proprietary technique. The tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The human hippocamps tissue total protein is provided in a buffer including HEPES (pH7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, Sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the hippocamps tissue pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The hippocamps tissue is then Western analyzed by either GAPDH or β-actin antibody, and the expression level is consistent with each lot.
Description: Human brain hippocamps tissue cytoplasmic protein lysate was prepared by isolating the cytoplasmic protein from whole tissue homogenates using a proprietary technique. The human hippocamps tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The cytoplasmic protein is provided in a buffer including HEPES (pH 7.9), MgCl2, KCl, EDTA, Sucrose, glycerol, and a cocktail of protease inhibitors. For quality control purposes, the isolated brain hippocamps tissue cytoplasmic protein pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The isolated brain hippocamps tissue cytoplasmic protein is then Western analyzed by GAPDH antibody, and the expression level is consistent with each lot.
Membrane Protein - Alzheimer's Disease:Brain: Amygdala
Description: Human brain amygdala tissue membrane protein lysate was prepared by isolating the membrane protein from whole tissue homogenates using a proprietary technique. The human amygdala tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The membrane protein is provided in a buffer including HEPES (pH 7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the isolated brain amygdala tissue membrane protein pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The isolated brain amygdala tissue membrane protein is then Western analyzed by either GAPDH or β-actin antibody to confirm there is no signal or very weak signal.
Description: Human brain temporal lobe tissue membrane protein lysate was prepared by isolating the membrane protein from whole tissue homogenates using a proprietary technique. The human temporal lobe tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The membrane protein is provided in a buffer including HEPES (pH 7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the isolated brain temporal lobe tissue membrane protein pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The isolated brain temporal lobe tissue membrane protein is then Western analyzed by either GAPDH or β-actin antibody to confirm there is no signal or very weak signal.
Description: Human brain hippocamps tissue membrane protein lysate was prepared by isolating the membrane protein from whole tissue homogenates using a proprietary technique. The human hippocamps tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The membrane protein is provided in a buffer including HEPES (pH 7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the isolated brain hippocamps tissue membrane protein pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The isolated brain hippocamps tissue membrane protein is then Western analyzed by either GAPDH or β-actin antibody to confirm there is no signal or very weak signal.
Description: Human pons tissue lysate was prepared by homogenization using a proprietary technique. The tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The human pons tissue total protein is provided in a buffer including HEPES (pH7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, Sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the pons tissue pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The pons tissue is then Western analyzed by either GAPDH or β-actin antibody, and the expression level is consistent with each lot.
Description: Human amygdala tissue lysate was prepared by homogenization using a proprietary technique. The tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The human amygdala tissue total protein is provided in a buffer including HEPES (pH7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, Sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the amygdala tissue pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The amygdala tissue is then Western analyzed by either GAPDH or β-actin antibody, and the expression level is consistent with each lot.
Description: Human thalamus tissue lysate was prepared by homogenization using a proprietary technique. The tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The human thalamus tissue total protein is provided in a buffer including HEPES (pH7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, Sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the thalamus tissue pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The thalamus tissue is then Western analyzed by either GAPDH or β-actin antibody, and the expression level is consistent with each lot.
Description: Human frontal lobe tissue lysate was prepared by homogenization using a proprietary technique. The tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The human frontal lobe tissue total protein is provided in a buffer including HEPES (pH7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, Sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the frontal lobe tissue pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The frontal lobe tissue is then Western analyzed by either GAPDH or β-actin antibody, and the expression level is consistent with each lot.
Description: Human parietal lobe tissue lysate was prepared by homogenization using a proprietary technique. The tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The human parietal lobe tissue total protein is provided in a buffer including HEPES (pH7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, Sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the parietal lobe tissue pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The parietal lobe tissue is then Western analyzed by either GAPDH or β-actin antibody, and the expression level is consistent with each lot.
Description: Human temporal lobe tissue lysate was prepared by homogenization using a proprietary technique. The tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The human temporal lobe tissue total protein is provided in a buffer including HEPES (pH7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, Sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the temporal lobe tissue pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The temporal lobe tissue is then Western analyzed by either GAPDH or β-actin antibody, and the expression level is consistent with each lot.
Description: Human occipital lobe tissue lysate was prepared by homogenization using a proprietary technique. The tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The human occipital lobe tissue total protein is provided in a buffer including HEPES (pH7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, Sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the occipital lobe tissue pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The occipital lobe tissue is then Western analyzed by either GAPDH or β-actin antibody, and the expression level is consistent with each lot.
Description: Human corpus Callosum tissue lysate was prepared by homogenization using a proprietary technique. The tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The human corpus Callosum tissue total protein is provided in a buffer including HEPES (pH7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, Sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the corpus Callosum tissue pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The corpus Callosum tissue is then Western analyzed by either GAPDH or β-actin antibody, and the expression level is consistent with each lot.
Description: Human precentral gyrus tissue lysate was prepared by homogenization using a proprietary technique. The tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The human precentral gyrus tissue total protein is provided in a buffer including HEPES (pH7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, Sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the precentral gyrus tissue pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The precentral gyrus tissue is then Western analyzed by either GAPDH or β-actin antibody, and the expression level is consistent with each lot.
cDNA - Human Adult Normal Tissue: Brain: Hippocampus
Description: Human postcentral gyrus tissue lysate was prepared by homogenization using a proprietary technique. The tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The human postcentral gyrus tissue total protein is provided in a buffer including HEPES (pH7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, Sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the postcentral gyrus tissue pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The postcentral gyrus tissue is then Western analyzed by either GAPDH or β-actin antibody, and the expression level is consistent with each lot.
Description: Human hippocamps tissue lysate was prepared by homogenization using a proprietary technique. The tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The human hippocamps tissue total protein is provided in a buffer including HEPES (pH7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, Sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the hippocamps tissue pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The hippocamps tissue is then Western analyzed by either GAPDH or β-actin antibody, and the expression level is consistent with each lot.
Description: Human brain hippocamps tissue cytoplasmic protein lysate was prepared by isolating the cytoplasmic protein from whole tissue homogenates using a proprietary technique. The human hippocamps tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The cytoplasmic protein is provided in a buffer including HEPES (pH 7.9), MgCl2, KCl, EDTA, Sucrose, glycerol, and a cocktail of protease inhibitors. For quality control purposes, the isolated brain hippocamps tissue cytoplasmic protein pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The isolated brain hippocamps tissue cytoplasmic protein is then Western analyzed by GAPDH antibody, and the expression level is consistent with each lot.
Description: Accumulation of the amyloid-β peptide (Aβ) in the cerebral cortex is a critical event in the pathogenesis of Alzheimer’s disease. The βamyloid protein precursor (APP) is cleaved by one of two βsecretases (BACE and BACE2), producing a soluble derivative of the protein and a membrane anchored 99-amino acid carboxy-terminal fragment (C99). The C99 fragment serves as substrate for βsecretase to generate the 4 kDa amyloid-β peptide (Aβ), which is deposited in the Alzheimer’s disease patients’ brains. BACE was identified by several groups independently and designated β-site APP cleaving enzyme (BACE) . BACE is a transmembrane aspartic protease and co-localizes with APP. BACE2 also cleaves APP at β-site and at a different site within Aβ. BACE2 locates on chromosome 21q22.3, the so-called ‘Down critical region’, suggesting that BACE2 and Aβ may also contribute to the pathogenesis of Down syndrome.;;For images please see PDF data sheet
Rat Hippocampus abundant transcript- like protein 1, Hiatl1 ELIS
Description: Accumulation of the amyloid-β peptide (Aβ) in the cerebral cortex is a critical event in the pathogenesis of Alzheimer’s disease. The β-amyloid protein precursor (APP) is cleaved by three enzymes (TACE, BACE/BACE2 and γ-secretase) at three distinct sites (α, β and γ respectively). The γ-secretase complex is a membrane-bound aspartyl protease that can cleave certain proteins at peptide bonds buried within the hydrophobic environment of the lipid bilayer and is composed of the proteins APH1, nicastrin, PEN2 and presenilin1. Its cleavage of APP results in either the non-toxic p3 (from the α and γ cleavage site) or the toxic Aβ (from the β and γ cleavage site). APH1 was initially identified as a component of the Notch pathway and exists in at least three distinct isoforms with APH1a as the principal isoform present in the γ-secretase complex. Mice deficient in this isoform, but not the other two, were lethal at E10.5, with impaired vascular and neural development observed. Besides acting as a critical component of the γ-secretase complex, nicastrin is also thought to be involved in cell proliferation and signaling, especially in regards to activation of Notch receptors as loss of nicastrin expression results in mouse embryonic lethality. Presenilin1 was initially identified a marker of susceptibility to early-onset Alzheimer’s disease.;;For images please see PDF data sheet
Description: Human pancreas tissue membrane protein lysate was prepared by isolating the membrane protein from whole tissue homogenates using a proprietary technique. The human pancreas tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The membrane protein is provided in a buffer including HEPES (pH 7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the isolated pancreas tissue membrane protein pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The isolated pancreas tissue membrane protein is then Western analyzed by either GAPDH or β-actin antibody to confirm there is no signal or very weak signal.
Description: Human lymphoma, Hodgkins Disease tissue membrane protein lysate was prepared by isolating the membrane protein from whole tissue homogenates using a proprietary technique. The human lymphoma, Hodgkins Disease tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The membrane protein is provided in a buffer including HEPES (pH 7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the isolated lymphoma, Hodgkins Disease tissue membrane protein pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The isolated lymphoma, Hodgkins Disease tissue membrane protein is then Western analyzed by either GAPDH or β-actin antibody to confirm there is no signal or very weak signal.
Description: human skeletal muscle tissue membrane protein lysate was prepared by isolating the membrane protein from whole tissue homogenates using a proprietary technique. The human skeletal muscle tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The membrane protein is provided in a buffer including HEPES (pH 7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the isolated Skeletal Muscle tissue membrane protein pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The isolated Skeletal Muscle tissue membrane protein is then Western analyzed by either GAPDH or β-actin antibody to confirm there is no signal or very weak signal.
Description: Human lymphoma, Non-Hodgkins Disease tissue membrane protein lysate was prepared by isolating the membrane protein from whole tissue homogenates using a proprietary technique. The human lymphoma, Non-Hodgkins Disease tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The membrane protein is provided in a buffer including HEPES (pH 7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the isolated lymphoma, Non-Hodgkins Disease tissue membrane protein pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The isolated lymphoma, Non-Hodgkins Disease tissue membrane protein is then Western analyzed by either GAPDH or β-actin antibody to confirm there is no signal or very weak signal.
Rat Alzheimer associated neuronal thread protein ELISA kit
Description: A competitive ELISA for quantitative measurement of Rat Alzheimer associated neuronal thread protein in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Rat Alzheimer associated neuronal thread protein ELISA kit
Description: A competitive ELISA for quantitative measurement of Rat Alzheimer associated neuronal thread protein in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Rat Alzheimer associated neuronal thread protein ELISA kit
Description: A competitive ELISA for quantitative measurement of Rat Alzheimer associated neuronal thread protein in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Pig Alzheimer associated neuronal thread protein ELISA kit
Description: A competitive ELISA for quantitative measurement of Porcine Alzheimer associated neuronal thread protein in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Pig Alzheimer associated neuronal thread protein ELISA kit
Description: A competitive ELISA for quantitative measurement of Porcine Alzheimer associated neuronal thread protein in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Pig Alzheimer associated neuronal thread protein ELISA kit
Description: A competitive ELISA for quantitative measurement of Porcine Alzheimer associated neuronal thread protein in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Dog Alzheimer associated neuronal thread protein ELISA kit
Description: A competitive ELISA for quantitative measurement of Canine Alzheimer associated neuronal thread protein in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Dog Alzheimer associated neuronal thread protein ELISA kit
Description: A competitive ELISA for quantitative measurement of Canine Alzheimer associated neuronal thread protein in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Dog Alzheimer associated neuronal thread protein ELISA kit
Description: A competitive ELISA for quantitative measurement of Canine Alzheimer associated neuronal thread protein in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
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Selection of participants supported biologically based largely on biomarkers of amyloid deposition, while the use of a biomarker as a result of the study largely depends on markers of neurodegeneration. Biomarkers play an important role in the design and conduction of research protocols targeting AD. However, their clinical validity, utility, and cost-effectiveness in the “real world” remains to be clarified.
