Fig. 4. Bexarotene interacts with Aβ42 aggregates through hydrogen bonding of its carboxyl group.

a AFM-IR spectrum of a bexarotene (Bex, green) film deposited on a gold substrate. We represent two spectra: (i) the average + SE of the raw spectra (n = 12), and (ii) the average + SE of the preprocessed spectra (n = 12) by applying an adjacent averaging filter (5 pts) and a Savitzky–Golay filter (second order, 15 pts). Five different raw spectra at each position (coloured crosses) were acquired. b Bexarotene alone has strong tendency to form dimers stabilised by two hydrogen bonds corresponding to a C = O IR absorption at 1690 cm⁻¹, compared to the 1720–1745 cm⁻¹ range of bexarotene forms with one hydrogen bond (Supplementary Fig. 9)⁴⁷. c Aβ42 fibrils show the typical spectrum of proteins (blue), while fibrils incubated with bexarotene (red) show an additional chemical signature related to the small molecule and with a frequency of absorption at ~1725 cm⁻¹, demonstrating that bexarotene is in the monomeric form and interacting with the fibrils through a single hydrogen bonding (red or orange). d Schematic of the fibril (blue) and bexarotene (green stars) interaction through hydrogen bonding. When bonded with the fibril or oligomer, bexarotene is likely to assume a conformation such that its bulky part is projected away from the nearest amino acid side chains.