Amyloid Beta - Explore the Science & Experts | ideXlab

Scan Science and Technology

Contact Leading Edge Experts & Companies

Amyloid Beta

The Experts below are selected from a list of 46626 Experts worldwide ranked by ideXlab platform

Amyloid Beta – Free Register to Access Experts & Abstracts

Avindra Nath – One of the best experts on this subject based on the ideXlab platform.

  • HIV-Tat Protein-Amyloid Beta Complex: From Molecular Interaction to Increased Neurotoxicity
    Biophysical Journal, 2015
    Co-Authors: Alina Hategan, Joseph P. Steiner, Mario A. Bianchet, Elena Karnaukhova, Emilios K. Dimitriadis, Avindra Nath

    Abstract:

    Since significant increase in Amyloid Beta plaque deposition was observed in HIV patients, it is important to examine the direct interaction between HIV-Tat protein, largely expressed by HIV virus after entering the cell, and Amyloid Beta molecules that aggregate and form the plaques. We investigated this interaction under physiological conditions starting with bulk methods and progressively zoomed in by using methods with fibrilar and molecular resolution. Circular dichroism of Amyloid Beta – Tat complexes revealed growth in Beta sheet structure and ThyT bulk fluorescence showed enhanced adhesion of aggregates to surfaces. Atomic force microscopy showed that the predominant typical singular uniform Amyloid fibrils turned into a population of double twisted fibrils followed by populations with predominantly thick unstructured filaments and aggregated large patches in a dose responsive manner, when HIV-Tat was present. The fibers break at regular intervals under air flow and the rupture length increased significantly with HIV-Tat presence, indicating greater mechanical resistance of fibrils. The period of the twists in the double fibrils grew with HIV-Tat indicating increased rigidity of the fibers. Single fibril fluorescence confirmed the external attachment of HIV-Tat to fibrils, which explains the lateral aggregation of fibrils into thick multifibrilar structures. Computer simulation indicated that Tat binds to the external side of the Amyloid Beta hairpin involving essentially the C terminal region of the Amyloid Beta chain. HIV-Tat presence in aggregates increases synergistically the neurotoxicity in primary neuronal cell cultures. Our data suggests that the major pathway towards cell damage is based on the increased rigidity and mechanical resistance of the Amyloid Beta-Tat complexes coupled with their stronger adhesion capacity due to Tat presence in the fibrils. Together, these can account for direct mechanical disruption through pore formation in the neuronal cell membranes.

  • HIV-Tat Protein Enhances Amyloid Beta Peptide Aggregation
    Biophysical Journal, 2014
    Co-Authors: Alina Hategan, Joseph P. Steiner, Emilios K. Dimitriadis, Avindra Nath

    Abstract:

    We show that Amyloid Beta 1-40 peptide aggregation under physiological conditions in the presence of HIV-Tat protein results in significant structural modifications. Atomic force microscopy imaging shows that the predominant typical singular uniform Amyloid fibrils that formed at a 200 micromolar concentration of Amyloid, turned into a population with more double twisted fibers when 0.08 micromolar HIV-Tat was present and at higher Tat concentrations (0.4 to 1.8 micromolar) it turned into populations with predominantly thick unstructured filaments and nonspecifically aggregated large patches. At a 1/10 molar ratio of HIV-Tat to Amyloid Beta peptide, the fibrils were much larger and irregular along the length, their dimensions being similar to those of Amyloid fibrils formed at extreme concentrations (>1 mM), but without the uniformly striated structure. The rupture length under air flow of filaments with similar dimensions increased significantly with the presence of HIV-tat protein at polymerization, suggesting internal structural changes within the filament backbone that lead to bigger mechanical resistance. Importantly, the presence of Tat in the Amyloid fibrils significantly increases the neurotoxicity of the fibrils, as shown in neuronal cell culture experiments. Future studies will involve localization of Tat molecules throughout the Amyloid filaments and aggregates, for a better understanding of the interaction between HIV-Tat protein and Amyloid Beta peptide.

Alina Hategan – One of the best experts on this subject based on the ideXlab platform.

  • HIV-Tat Protein-Amyloid Beta Complex: From Molecular Interaction to Increased Neurotoxicity
    Biophysical Journal, 2015
    Co-Authors: Alina Hategan, Joseph P. Steiner, Mario A. Bianchet, Elena Karnaukhova, Emilios K. Dimitriadis, Avindra Nath

    Abstract:

    Since significant increase in Amyloid Beta plaque deposition was observed in HIV patients, it is important to examine the direct interaction between HIV-Tat protein, largely expressed by HIV virus after entering the cell, and Amyloid Beta molecules that aggregate and form the plaques. We investigated this interaction under physiological conditions starting with bulk methods and progressively zoomed in by using methods with fibrilar and molecular resolution. Circular dichroism of Amyloid Beta – Tat complexes revealed growth in Beta sheet structure and ThyT bulk fluorescence showed enhanced adhesion of aggregates to surfaces. Atomic force microscopy showed that the predominant typical singular uniform Amyloid fibrils turned into a population of double twisted fibrils followed by populations with predominantly thick unstructured filaments and aggregated large patches in a dose responsive manner, when HIV-Tat was present. The fibers break at regular intervals under air flow and the rupture length increased significantly with HIV-Tat presence, indicating greater mechanical resistance of fibrils. The period of the twists in the double fibrils grew with HIV-Tat indicating increased rigidity of the fibers. Single fibril fluorescence confirmed the external attachment of HIV-Tat to fibrils, which explains the lateral aggregation of fibrils into thick multifibrilar structures. Computer simulation indicated that Tat binds to the external side of the Amyloid Beta hairpin involving essentially the C terminal region of the Amyloid Beta chain. HIV-Tat presence in aggregates increases synergistically the neurotoxicity in primary neuronal cell cultures. Our data suggests that the major pathway towards cell damage is based on the increased rigidity and mechanical resistance of the Amyloid Beta-Tat complexes coupled with their stronger adhesion capacity due to Tat presence in the fibrils. Together, these can account for direct mechanical disruption through pore formation in the neuronal cell membranes.

  • HIV-Tat Protein Enhances Amyloid Beta Peptide Aggregation
    Biophysical Journal, 2014
    Co-Authors: Alina Hategan, Joseph P. Steiner, Emilios K. Dimitriadis, Avindra Nath

    Abstract:

    We show that Amyloid Beta 1-40 peptide aggregation under physiological conditions in the presence of HIV-Tat protein results in significant structural modifications. Atomic force microscopy imaging shows that the predominant typical singular uniform Amyloid fibrils that formed at a 200 micromolar concentration of Amyloid, turned into a population with more double twisted fibers when 0.08 micromolar HIV-Tat was present and at higher Tat concentrations (0.4 to 1.8 micromolar) it turned into populations with predominantly thick unstructured filaments and nonspecifically aggregated large patches. At a 1/10 molar ratio of HIV-Tat to Amyloid Beta peptide, the fibrils were much larger and irregular along the length, their dimensions being similar to those of Amyloid fibrils formed at extreme concentrations (>1 mM), but without the uniformly striated structure. The rupture length under air flow of filaments with similar dimensions increased significantly with the presence of HIV-tat protein at polymerization, suggesting internal structural changes within the filament backbone that lead to bigger mechanical resistance. Importantly, the presence of Tat in the Amyloid fibrils significantly increases the neurotoxicity of the fibrils, as shown in neuronal cell culture experiments. Future studies will involve localization of Tat molecules throughout the Amyloid filaments and aggregates, for a better understanding of the interaction between HIV-Tat protein and Amyloid Beta peptide.

Inga Kadish – One of the best experts on this subject based on the ideXlab platform.

  • Deposition of mouse Amyloid Beta in human APP/PS1 double and single AD model transgenic mice.
    Neurobiology of disease, 2006
    Co-Authors: Thomas Van Groen, Amanda J. Kiliaan, Inga Kadish

    Abstract:

    The deposition of Amyloid Beta (ABeta) peptides and neurofibrillary tangles are the two characteristic pathological features of Alzheimer’s disease (AD). To investigate the relation between Amyloid precursor protein (APP) production, Amyloid Beta deposition and the type of ABeta in deposits, i.e., human and/or mouse, we performed a histopathological analysis, using mouse and human specific antibodies, of the neocortex and hippocampus in 6, 12 and 19 months old APP/PS1 double and APP and PS1 single transgenic mice. There was a significant correlation between the human Amyloid Beta deposits and the intrinsic rodent Amyloid Beta deposits, that is, all plaques contained both human and mouse ABeta, and the diffuse Amyloid Beta deposits also colocalized human and mouse ABeta. Furthermore, some blood vessels (mainly leptomeningeal vessels) show labeling with human ABeta, and most of these vessels also label with mouse ABeta. Our findings demonstrate that the human Amyloid deposits in APP/PS1 transgenic mice are closely associated with mouse ABeta, however, they do not precisely overlap. For instance, the core of plaques consists of primarily human ABeta, whereas the rim of the plaque contains both human and mouse Amyloid Beta, similarly, human and mouse ABeta are differentially localized in the blood vessel wall. Finally, as early as Amyloid Beta deposits can be detected, they show the presence of both human and mouse ABeta. Together, these data indicate that mouse ABeta is formed and deposited in significant amounts in the AD mouse brain and that it is deposited together with the human ABeta.