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Anti-Abeta antibodiesAmyloid BetaNeuronsAntibodiesAggregationAlzheimer'sDepositionPeptidesPlaquesHypothesisTransgenicProteinPathologyPreclinicalMoleculesMutationsTherapeuticMolecularBrainMechanismFormationArticleAmyloidOligomersAccumulationOligomericDepositsTg2576CognitivePlasmaCreateSignificantResearch
Anti-Abeta antibodies1
  • These insights reveal a differentiating biological property of PBD-C06 compared to other anti-Abeta antibodies and further support the development of PBD-C06. (vivoryon.com)
Amyloid Beta4
  • Antibodies directed against Amyloid Beta (Abeta) are able to successfully clear plaques and reverse cognitive deficits in mouse models. (polyplus-sartorius.com)
  • All recognized mutations for AD are associated with increased deposition of amyloid-beta (Abeta), a peptide fragment comprising 39-43 amino acids that derive from the catabolism of the amyloid precursor protein (APP) molecule. (medscape.com)
  • The aggregation of the protein Amyloid-beta (Abeta) into plaques outside the nerve cells has been recognized in patients with Alzheimer's disease since 1905. (lu.se)
  • The majority of researchers agree that Amyloid-beta (Abeta) matters for Alzheimer's disease. (lu.se)
Neurons5
  • BACE1 is the major beta-secretase for generation of Abeta peptides by neurons. (alzforum.org)
  • We then looked in mice with AD mutations where we also had accelerated the Abeta aggregation and found lots of aggregated Abeta inside the neurons at the first time points. (lu.se)
  • But as soon as the Abeta plaques started to accumulate outside the neurons, these pools of aggregated Abeta inside the neurons almost disappeared. (lu.se)
  • Initially, before plaques are formed, the neurons may just overproduce Abeta and this leads to aggregation inside the cells. (lu.se)
  • So, you think that aggregation of Abeta inside the neurons may be essential for Alzheimer's pathology, but how do prion-like properties come into the picture, as the title of your thesis indicates? (lu.se)
Antibodies2
  • Specific targeting of pGlu-Abeta with antibodies could eliminate neurotoxic pGlu-Abeta containing oligomers in the brain. (vivoryon.com)
  • The Company has medical use and composition of matter patents related to the inhibition of QC and anti-pGlu-Abeta-specific monoclonal antibodies, and has, in the Company's view, a leading position in this field of research. (vivoryon.com)
Aggregation2
  • The results explain why the unique structure of pGlu-Abeta can facilitate enhanced aggregation of Abeta oligomers. (vivoryon.com)
  • Here, he explains where he thinks Abeta aggregation begins. (lu.se)
Alzheimer's3
  • Alzheimer's Research & Therapy is now accepting research submissions for consideration in a special series on abeta catabolism , planned for publication in late 2013. (biomedcentral.com)
  • We welcome research manuscripts to accompany a series of articles reviewing the evidence for decreased Abeta clearance in Alzheimer's disease (AD), describing the proteases known to degrade the peptide, and addressing how familial AD mutations and late-onset AD risk factors may act, at least in part, by altering Abeta clearance. (biomedcentral.com)
  • The Abeta plaques are a pathological hallmark of Alzheimer's disease, Abeta is the first biomarker that is altered, heritable forms of Alzheimer's rely on mutations in the Abeta protein* or enzymes involved in its production, and a mutation that reduces Abeta production protects against AD. (lu.se)
Deposition1
  • Human APOE4 increases microglia reactivity at Abeta plaques in a mouse model of Abeta deposition. (lu.se)
Peptides2
  • The studies revealed a unique binding mode of PBD-C06 to pGlu-Abeta peptides, which are believed to catalyze the seeding of synapto/neurotoxic Abeta oligomers, a key culprit in the pathology of AD. (vivoryon.com)
  • Furthermore, the data provide a rationale for the high target specificity of PBD-C06 and suggest low binding to off-targets, such as unmodified, less toxic Abeta peptides. (vivoryon.com)
Plaques3
  • This translated into 3D6 effectively clearing plaques and reducing the levels of insoluble Abeta, whilst chGantenerumab and mC2 did not. (polyplus-sartorius.com)
  • Still, Abeta plaques do not correlate to cognitive decline and removing plaques have not improved symptoms in clinical trials. (lu.se)
  • Hence, plaques sucking Abeta out of the cells may trigger even more production of that protein in a vicious cycle. (lu.se)
Hypothesis3
  • The hypothesis being tested is that different human apoE isoforms and lipidation states of apoE alters apoE and Abeta clearance in the CNS. (brightfocus.org)
  • The positive effects seen on secondary exploratory efficacy markers are strongly supporting (a) the hypothesis of pGlu-Abeta being synaptotoxic and (b) the therapeutic concept pursued by Probiodrug. (vivoryon.com)
  • There is also a hypothesis that Abeta aggregates can spread in a prion-like way. (lu.se)
Transgenic1
Protein2
  • Some of you may be annoyed by the fact I call Abeta a protein, and yes, indeed, it is a peptide, but let's just simplify it, calling it a protein for now. (lu.se)
  • A wel -known example is Alzheimers disease, which is a amyloid disease caused by fibril formation of a protein cal ed Abeta. (lu.se)
Pathology1
  • The development approaches are targeting a key neuro/synaptotoxic component of the pathology, pyroglutamate-Abeta (pGlu-Abeta, N3pG) as a therapeutic strategy. (vivoryon.com)
Preclinical1
  • Probiodrug is progressing two complementary strategies for tackling pGlu-Abeta with two candidates in development: PQ912, a small molecule inhibitor of Glutaminyl Cyclase, now in Phase 2, and PBD-C06, a pGlu-Abeta-specific monoclonal antibody in preclinical stage. (vivoryon.com)
Molecules2
  • Chemically, what makes Abeta prone to aggregate is when the concentration of the molecules is high and the pH is rather low. (lu.se)
  • Later, when Abeta also accumulates in critical amounts outside the cells, this may suck out the internal Abeta, like osmosis of molecules over a membrane to have equal concentrations on both sides. (lu.se)
Mutations1
  • We looked at this both in cultured cell lines as well as in mouse models carrying mutations in the Abeta gene. (lu.se)
Therapeutic2
  • Novel therapies aimed at increasing Abeta clearance have already been shown to be effective in mouse models, and new therapeutic targets will undoubtedly emerge as the full range of clearance mechanisms in the brain is fully characterized. (biomedcentral.com)
  • In these studies, the binding characteristics of a murine version of Probiodrug's lead therapeutic antibody (PBD-C06) against its designated target pGlu-Abeta was analyzed at the molecular level applying co-crystallization and X-ray structure analysis. (vivoryon.com)
Molecular1
  • A large amount of evidence suggests that apoE is likely to influence risk for AD by acting as a molecular chaperone for Abeta and influencing Abeta fibrillogenesis and clearance. (brightfocus.org)
Brain3
  • We further hypothesize that the perturbation in regulation of apoE metabolism will then influence Abeta metabolism and will alter both the time course and amount of Abeta depostion in brain. (brightfocus.org)
  • Defects in clearance of Abeta from brain could underline many cases of sporadic AD. (brightfocus.org)
  • Meaning that Abeta can misfold/aggregate in a specific way where the misfolded Abeta can induce healthy Abeta to also misfold, thereby spreading the disease throughout the brain. (lu.se)
Mechanism1
Formation2
  • Complementary to the small molecule PQ912 inhibiting the formation of the synaptotoxic agent pGlu-Abeta, the company is developing PBD-C06, an anti-pGlu-Abeta-specific monoclonal antibody. (vivoryon.com)
  • First, we showed that one could induce the formation of prion-like Abeta inside a cell, something that had never been shown before. (lu.se)
Article1
  • Please submit online and indicate in your covering letter that you would like the article to be considered for the abeta catabolism series. (biomedcentral.com)
Amyloid7
  • Amyloid deposits, also called plaques, of Alzheimer's patients consist of several protein components like the a myloid beta -peptides ( Abeta , Aβ ) 1-40/42 and additional C- and N-terminally truncated and modified fragments. (sysy.com)
  • More in-depth studies will clarify whether enhancers of expression of specific apoE isoforms may indeed represent a new preventive/therapeutic approach for diseases associated with toxic accumulation of amyloid and Abeta peptides in humans. (medscape.com)
  • Armstrong, RA 1996, ' Beta-amyloid (Abeta) deposits and blood vessels: laminar distribution in the frontal cortex of patients with Alzheimer's disease ', Neuroscience Research Communications , vol. 18, no. 1, pp. 19-28. (aston.ac.uk)
  • IL-6, hsCRP), and beta amyloid metabolites (abeta 40 and 42). (nih.gov)
  • Previous studies by Bayer's laboratory showed that inhibiting enzymatic CaMKII activity protects against some of the effects of amyloid-beta (Abeta) plaques in the brain, a hallmark of Alzheimer's disease (AD). (neurosciencenews.com)
  • Mutation of the signal or depletion of cellular mu4 shift the steady-state localization of APP from endosomes to the TGN, and enhance amyloidogenic processing of APP to the pathogenic amyloid-beta (Abeta) peptide. (nih.gov)
  • Although the presence of plaques of fibrillar aggregates of the amyloid beta peptide (Abeta) is a signature of AD, evidence suggests that the preplaque small oligomeric Abeta promotes both synaptic dysfunction and neuronal death. (nih.gov)
Oligomers1
  • Furthermore, Tg2576 mice display Abeta oligomers and reduced pCREB in the CNS, which is normalized by CaN inhibition. (nih.gov)
Accumulation3
  • In contrast to extracellular plaques that do not perfectly correlate with Alzheimer´s disease intraneuronal Abeta accumulation and vascular Abeta deposits have gained more and more evidence to be among the crucial factors responsible for progressive neuron loss. (sysy.com)
  • ApoE2, on the other hand, induced a marked decrease in Abeta accumulation, as shown by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). (medscape.com)
  • The [genetic] mutation causes a more rapid accumulation of ABeta in the brains of people who have it. (time.com)
Oligomeric3
  • Recognizes specific oligomeric structures formed preferentially by Abeta-pE3. (sysy.com)
  • To investigate this issue, we compared the effect of monomeric, oligomeric, and fibrillar Abeta on CaN activity, CaN-dependent pCREB and phosphorylated Bcl-2 Associated death Protein (pBAD) levels, and cell death in SY5Y cells and in rat brain slices, and determined the role of CaN on CREB phosphorylation in the CNS of Tg2576 mice. (nih.gov)
  • Our results show that oligomeric Abeta specifically induces CaN activity and promotes CaN-dependent CREB and Bcl-2 Asociated death Protein (BAD) dephosphorylation and cell death. (nih.gov)
Deposits2
  • Further experiments were conducted by expressing apoE with lentiviral vectors in PDAPP/ApoE-knockout mice that develop Abeta deposits with aging. (medscape.com)
  • In most patients, the density of the diffuse and primitive Abeta deposits was greatest in the upper cortical layers and the classic deposits in the deeper cortical layers. (aston.ac.uk)
Tg25761
  • 13. Immunotherapy against APP beta-secretase cleavage site improves cognitive function and reduces neuroinflammation in Tg2576 mice without a significant effect on brain abeta levels. (nih.gov)
Cognitive1
  • Combination anti-Abeta treatment maximizes cognitive recovery and rebalances mTOR signaling in APP mice. (mayo.edu)
Plasma1
  • 2007 . The influence of diagnosis, intra- and inter-person variability on serum and plasma Abeta levels. (nih.gov)
Create1
  • Abeta version to create VR productions is also available. (ijnet.org)
Significant1
  • Multiple regression analysis selected vertical distance below the pia mater as the most significant factor correlated with the Abeta deposit density. (aston.ac.uk)
Research1
  • It activates the enzyme that produces the ABeta," Richard Scheller, executive vice president of research and development at Genentech, told ABC. (time.com)