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HIV-Tat protein enhances amyloid beta peptide aggregation and neurotoxicity

Monday, September 22, 2014 — Poster Session I

12:00 p.m. – 2:00 p.m.

FAES Academic Center



* FARE Award Winner


  • A. Popescu Hategan
  • J. Steiner
  • E. Karnaukhova
  • E. Dimitriadis
  • A. Nath


We show that amyloid beta 1-40 peptide aggregation under physiological conditions in the presence of HIV-Tat protein results in significant structural changes. Atomic force microscopy imaging 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 0.08-1.8 micromolar HIV-Tat was present. The rupture length under air flow of fibrils increased significantly with HIV-Tat at polymerization, indicating greater mechanical resistance of fibrils. The distance between successive twists in the twisted double fibrils grew with HIV-Tat showing increased rigidity of fibers. Circular dichroism of of amyloid beta - Tat complexes revealed growth in beta sheet structure and ThyT bulk fluorescence showed enhanced adhesion of aggregates to surfaces. Anti-HIV-Tat antibody binding to amyloid beta - Tat complexes confirmed the external attachment of Tat to fibrils, which accounts for lateral aggregation of fibrils into thick multifibrilar structures. The presence of HIV-Tat in the amyloid fibrils significantly increased their neurotoxicity in primary neuronal cell cultures. The increased rigidity of amyloid beta - Tat fibrils together with their larger adhesion capacity may account for mechanical disruption of the neuronal cell membranes.

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