Synchrotron FTIR reveals lipid around and within amyloid plaques in transgenic mice and Alzheimer's disease brain

Abstract

While the basis of neuronal degeneration in Alzheimer's disease (AD) continues to be debated, the amyloid cascade hypothesis remains central. Amyloid plaques are a required pathological marker for post mortem diagnosis, and Aβ peptide is regarded by most as a critical trigger at the very least. We present spectrochemical image analysis of brain tissue sections obtained with the mid-infrared beamline IRENI (InfraRed ENvironmental Imaging, Synchrotron Radiation Center, U Wisconsin-Madison), where the pixel resolution of 0.54 × 0.54 µm(2) permits analysis at sub-cellular dimensions. Spectrochemical images of dense core plaque found in hippocampus and cortex sections of two transgenic mouse models of AD (TgCRND8 and 3×Tg) are compared with plaque images from a 91 year old apoE43 human AD case. Spectral analysis was done in conjunction with histochemical stains of serial sections. A lipid membrane-like spectral signature surrounded and infiltrated the dense core plaques in all cases. Remarkable compositional similarities in early stage plaques suggest similar routes to plaque formation, regardless of genetic predisposition or mammalian origin.

TREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy

“…Given the recent findings that Trem2 recognizes various types of lipids that are present in amyloid plaques (Wang et al, 2015), we postulate that the extent and types of lipids decorating the plaque surface may regulate the microglia barrier through Trem2 signaling. Consistent with this hypothesis, microglia around diffuse plaques do not have a very activated and polarized morphology (Figure 6), and spectrochemical analysis shows that diffuse plaques do not have prominent lipid coating on their surface (Liao et al, 2013; Rak et al, 2007). In contrast, as amyloid deposits become filamentous and thioflavin S positive, which likely makes them more lipophilic (Hilbich et al, 1992), they robustly attract microglia processes, consistent with recent in vivo imaging studies (Jung et al, 2015).…”

Formation of Dynamic Soluble Surfactant-induced Amyloid β Peptide Aggregation Intermediates

“…Surfactants may also be considered as a model system for natural lipids that were found to be located around and within in vivo amyloid plaques (13,14) and revert A␤(1-42) aggregates to neurotoxic protofibrils (15). This underlines the significant role of lipids in the aggregation process.…”

“…Lipids are known to be associated with in vivo amyloid plaques (13,14). Several studies have also been devoted to the effects of lipids on A␤ aggregation pathways (15,16).…”

The relationship between iron dyshomeostasis and amyloidogenesis in Alzheimer's disease: Two sides of the same coin

“…Seeded plaques can sequester other metals (Zn, Cu, Al, Mn) and a variety of cellular products, such as lipids, impairing proper cellular function 60,61 . Aβ 42 is increased with APP expression or BACE-1 activity or decreased ADAM activity.…”