Dense‐core and diffuse Aβ plaques in TgCRND8 mice studied with synchrotron FTIR microspectroscopy

Plaques composed of the Aβ peptide are the main pathological feature of Alzheimer's disease. Dense‐core plaques are fibrillar deposits of Aβ, showing all the classical properties of amyloid including β‐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 β‐sheet conformation. The amide I maximum of plaque cores was at 1623 cm−1, and unlike for in vitro Aβ fibrils, the high‐frequency (1680–1690 cm−1) component attributed to antiparallel β‐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. © 2007 Wiley Periodicals, Inc. Biopolymers 87: 207–217, 2007. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com