In situ characterization of beta-amyloid in Alzheimer's diseased tissue by synchrotron Fourier transform infrared Microspectroscopy

被引:189
作者
Choo, LP
Wetzel, DL
Halliday, WC
Jackson, M
LeVine, SM
Mantsch, HH
机构
[1] NATL RES COUNCIL CANADA,INST BIODIAGNOST,WINNIPEG,MB R3B 1Y6,CANADA
[2] UNIV MANITOBA,DEPT BIOCHEM & MOL BIOL,WINNIPEG,MB,CANADA
[3] KANSAS STATE UNIV,MICROBEAM MOL SPECT LAB,MANHATTAN,KS 66506
[4] HLTH SCI CTR,DEPT PATHOL,WINNIPEG,MB,CANADA
[5] UNIV KANSAS,MED CTR,DEPT PHYSIOL,KANSAS CITY,KS 66103
关键词
D O I
10.1016/S0006-3495(96)79411-0
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
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 tissue. Using a Fourier transform infrared microspectroscopic technique, areas of interest can be selected for spectral measurements with regions 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-quality 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 infrared radiation provided by a synchrotron light source (National Synchrotron Light Source, Brookhaven National Laboratories), using aperture sizes as small as 12 mu m x 12 mu m. This allowed spectroscopic mapping of brain tissue regions containing amyloid. We observe that in situ proteins of grey matter exist predominantly in an alpha-helical and/or unordered conformation, whereas within amyloid deposits a beta-sheet structure predominates. The hydrogen bonding strength of the beta-structure found in situ is different from that reported in the literature for isolated/chemically synthesized beta-amyloid peptides.
引用
收藏
页码:1672 / 1679
页数:8
相关论文
共 28 条
[1]   SOLUTION STRUCTURES OF BETA PEPTIDE AND ITS CONSTITUENT FRAGMENTS - RELATION TO AMYLOID DEPOSITION [J].
BARROW, CJ ;
ZAGORSKI, MG .
SCIENCE, 1991, 253 (5016) :179-182
[2]   INFRARED SPECTROSCOPIC CHARACTERIZATION OF MULTIPLE-SCLEROSIS PLAQUES IN THE HUMAN CENTRAL-NERVOUS-SYSTEM [J].
CHOO, LP ;
JACKSON, M ;
HALLIDAY, WC ;
MANTSCH, HH .
BIOCHIMICA ET BIOPHYSICA ACTA, 1993, 1182 (03) :333-337
[3]   INFRARED-SPECTRA OF HUMAN CENTRAL-NERVOUS-SYSTEM TISSUE - DIAGNOSIS OF ALZHEIMERS-DISEASE BY MULTIVARIATE ANALYSES [J].
CHOO, LP ;
MANSFIELD, JR ;
PIZZI, N ;
SOMORJAI, RI ;
JACKSON, M ;
HALLIDAY, WC ;
MANTSCH, HH .
BIOSPECTROSCOPY, 1995, 1 (02) :141-148
[4]   SYNTHETIC POSTTRANSLATIONALLY MODIFIED HUMAN A-BETA PEPTIDE EXHIBITS A MARKEDLY INCREASED TENDENCY TO FORM BETA-PLEATED SHEETS IN-VITRO [J].
FABIAN, H ;
SZENDREI, GI ;
MANTSCH, HH ;
GREENBERG, BD ;
OTVOS, L .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1994, 221 (03) :959-964
[5]   INFRARED SPECTROSCOPIC CHARACTERIZATION OF ALZHEIMER PLAQUES [J].
FABIAN, H ;
CHOO, LP ;
SZENDREI, GI ;
JACKSON, M ;
HALLIDAY, WC ;
OTVOS, L ;
MANTSCH, HH .
APPLIED SPECTROSCOPY, 1993, 47 (09) :1513-1518
[6]   CONFORMATION AND FIBRILLOGENESIS OF ALZHEIMER A-BETA PEPTIDES WITH SELECTED SUBSTITUTION OF CHARGED RESIDUES [J].
FRASER, PE ;
MCLACHLAN, DR ;
SUREWICZ, WK ;
MIZZEN, CA ;
SNOW, AD ;
NGUYEN, JT ;
KIRSCHNER, DA .
JOURNAL OF MOLECULAR BIOLOGY, 1994, 244 (01) :64-73
[7]   FIBRIL FORMATION BY PRIMATE, RODENT, AND DUTCH-HEMORRHAGIC ANALOGS OF ALZHEIMER AMYLOID BETA-PROTEIN [J].
FRASER, PE ;
NGUYEN, JT ;
INOUYE, H ;
SUREWICZ, WK ;
SELKOE, DJ ;
PODLISNY, MB ;
KIRSCHNER, DA .
BIOCHEMISTRY, 1992, 31 (44) :10716-10723
[8]   BIOCHEMISTRY OF ALZHEIMERS-DISEASE AMYLOID PLAQUES [J].
FRASER, PE ;
LEVESQUE, L ;
MCLACHLAN, DR .
CLINICAL BIOCHEMISTRY, 1993, 26 (05) :339-349
[9]   PH-DEPENDENT STRUCTURAL TRANSITIONS OF ALZHEIMER AMYLOID PEPTIDES [J].
FRASER, PE ;
NGUYEN, JT ;
SUREWICZ, WK ;
KIRSCHNER, DA .
BIOPHYSICAL JOURNAL, 1991, 60 (05) :1190-1201
[10]  
HILL SL, 1989, P SOC PHOTO-OPT INS, V1145, P400