IN-SITU CHARACTERIZATION OF BETA-AMYLOID IN ALZHEIMERS DISEASED TISSUE BY SYNCHROTRON FOURIER-TRANSFORM INFRARED MICROSPECTROSCOPY

We report the first evidence of the structure of P-amyloid protein as it exists in situ within a slice of human Alzheimer's diseased brain t issue. Using a Fourier transform infrared microspectroscopic technique , areas of interest can be selected for spectral measurements with reg ions of potential contamination masked. In so doing, it is possible to obtain infrared spectra only of beta-amyloid and not the surrounding grey matter within which it lies. However, to obtain spectra of high-q uality signal-to-noise ratio using a conventional infrared source, we were limited to aperture sizes between 24 mu m x 24 mu m to 50 mu m x 50 mu m. Markedly improved high-quality spectra were acquired with inf rared radiation provided by a synchrotron light source (National Synch rotron Light Source, Brookhaven National Laboratories), using aperture sizes as small as 12 mu m x 12 mu m. This allowed spectroscopic mappi ng of brain tissue regions containing amyloid. We observe that in situ proteins of grey matter exist predominantly in an alpha-helical and/o r unordered conformation, whereas within amyloid deposits a beta-sheet structure predominates. The hydrogen bonding strength of the beta-str ucture found in situ is different from that reported in the literature for isolated/chemically synthesized beta-amyloid peptides.