Article

X-ray diffraction from intact tau aggregates in human brain tissue

DePaul University, Department of Physics, 2219 N. Kenmore Ave., Chicago, IL 60614.
Nuclear Instruments and Methods in Physics Research Section A Accelerators Spectrometers Detectors and Associated Equipment (Impact Factor: 1.32). 09/2011; 649(1):184-187. DOI: 10.1016/j.nima.2011.01.059
Source: PubMed

ABSTRACT We describe an instrument to record x-ray diffraction patterns from diseased regions of human brain tissue by combining an in-line visible light fluorescence microscope with an x-ray diffraction microprobe. We use thiazine red fluorescence to specifically label and detect the filamentous tau protein pathology associated with Pick's disease, as several labs have done previously. We demonstrate that thiazine red-enhanced regions within the tissue show periodic structure in x-ray diffraction that is not observed in healthy tissue. One observed periodicity (4.2 Å) is characteristic of cross-beta sheet structure, consistent with previous results from powder diffraction studies performed on purified, dried tau protein.

Download full-text

Full-text

Available from: Thomas C Irving, Jun 27, 2015
0 Followers
 · 
132 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The 18ID undulator beamline of the Biophysics Collaborative Access Team at the Advanced Photon Source, Argonne, IL, USA, is a high-performance instrument designed for, and dedicated to, the study of partially ordered and disordered biological materials using the techniques of small-angle X-ray scattering, fiber diffraction, and X-ray absorption spectroscopy. The beamline and associated instrumentation are described in detail and examples of the representative experimental results are presented.
    Journal of Synchrotron Radiation 10/2004; 11(Pt 5):399-405. DOI:10.1107/S0909049504016760 · 3.02 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We have studied the conformation of tau protein and Alzheimer paired helical filaments (PHF) by several spectroscopic, scattering, and imaging methods revealing the overall shape and the conformation of the polypeptide backbone. Tau protein behaves in solution as if it were denatured; no evidence for compact folding was detected. The protein is highly extended, there is no defined radius of gyration, and the scattering is best described by that of a random ("Gaussian") polymer. CD and Fourier transform infrared spectroscopy show only a minimal content of ordered secondary structure (alpha-helix or beta-sheet). Similarly, PHFs from Alzheimer brain tissue show no detectable secondary structure by x-ray diffraction or spectroscopy. It is thus unlikely that the aggregation of tau into Alzheimer PHFs is based on interactions between strands of beta-sheets (a model currently favored for other disease-related polymers such as beta-amyloid fibers of Alzheimer's disease).
    Journal of Biological Chemistry 10/1994; 269(39):24290-7. · 4.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abundant tau-positive neurofibrillary lesions constitute a defining neuropathological characteristic of Alzheimer's disease. Filamentous tau pathology is also central to a number of other dementing disorders, such as Pick's disease, progressive supranuclear palsy, corticobasal degeneration and familial frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). The discovery of mutations in the tau gene in FTDP-17 has firmly established the relevance of tau pathology for the neurodegenerative process. Experimental studies have provided a system for the assembly of full-length tau into Alzheimer-like filaments, providing an assay for the testing of compounds that inhabit the formation of tau filaments.Trends Neurosci. (1998) 21, 428–433
    Trends in Neurosciences 11/1998; DOI:10.1016/S0166-2236(98)01337-X · 12.90 Impact Factor