Dense-core and diffuse Abeta plaques in TgCRND8 mice studied with synchrotron FTIR microspectroscopy.
Plaques composed of the Abeta peptide are the main pathological feature of Alzheimer's disease. Dense-core plaques are fibrillar deposits of Abeta, showing all the classical properties of amyloid including beta-sheet secondary structure, while diffuse plaques are amorphous deposits. We studied both plaque types, using synchrotron infrared (IR) microspectroscopy, a technique that allows the chemical composition and average protein secondary structure to be investigated in situ. We examined plaques in hippocampal, cortical and caudal tissue from 5- to 21-month-old TgCRND8 mice, a transgenic model expressing doubly mutant amyloid precursor protein, and displaying impaired hippocampal function and robust pathology from an early age. Spectral analysis confirmed that the congophilic plaque cores were composed of protein in a beta-sheet conformation. The amide I maximum of plaque cores was at 1623 cm(-1), and unlike for in vitro Abeta fibrils, the high-frequency (1680-1690 cm(-1)) component attributed to antiparallel beta-sheet was not observed. A significant elevation in phospholipids was found around dense-core plaques in TgCRND8 mice ranging in age from 5 to 21 months. In contrast, diffuse plaques were not associated with IR detectable changes in protein secondary structure or relative concentrations of any other tissue components.
Department of Chemistry, University of Manitoba, Winnipeg, MB, Canada R3T 2N2.
Margaret
M
Rak
Marc R
MR
Del Bigio
Sabine
S
Mai
David
D
Westaway
Kathleen
K
Gough
D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000737:chemistry* / Q000235:genetics; D000818:Animals; D001923:Brain Chemistry; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D017356:Synchrotrons
D016229:Amyloid beta-Peptides