Detection of Aβ plaque-associated astrogliosis in Alzheimer's disease brain by spectroscopic imaging and immunohistochemistry

Abstract

Correlative vibrational spectroscopy and immunohistochemistry reveal astroglial processes co-localised with the lipid-rich shell of Aβ plaques.

The search for a unique Raman signature of amyloid-beta plaques in human brain tissue from Alzheimer's disease patients

“…Additionally, this could put the tissue under stress in terms of heat and deformation, which potentially alters the tissue structure or even leads to total tissue loss. Therefore, techniques such as FTIR-spectroscopy, 21 Raman spectroscopy [22][23][24] and its derivatives coherent anti-Stokes Raman scattering (CARS), stimulated Raman scattering (SRS) and surface-enhanced Raman spectroscopy (SERS) 17,18,25 could offer a label-free and non-destructive characterization of the morphology of the tissue. Together with optical coherence tomography, 26,27 these techniques could overcome the disadvantages of the staining procedure.…”

“…22,24,32,33 Literature suggests that the peak intensity at 1669 cm −1 (β-sheet) or the peak ratio between β-sheet and lipids (1669 cm −1 to 1445 cm −1 ) increases when measuring inside an amyloid plaque. 22,33,34 Furthermore, recent Alzheimer related publications on mouse brain tissue suggest that a lipid ring (halo) surrounds the plaque location, 18,21 while others found lipids and lipofuscin co-localized with plaques in human brain tissue. 16,17 In a recent study, Michael et al presented Raman spectral data (λ = 647.1 nm) from a tiny diseased human brain tissue area of 30 × 30 µm, barely matching the size of a plaque.…”

Hyperspectral analysis applied to micro-Brillouin maps of amyloid-beta plaques in Alzheimer's disease brains

“…1 shows bright-field reflection and Brillouin images of amyloid plaques in transgenic mouse brain sections, whereby the plaque core is easily recognizable from the elevated frequency of the Brillouin peak. This has previously been shown to correspond to the intermolecular β-sheets of the aggregated Aβ peptide detected by FTIR and Raman spectroscopy applied to the same tissue sections 4…”

“…For biomedical applications, this is a particularly pressing issue. In Aβ plaques for which we have demonstrated the mechanical heterogeneity in a mouse model of amyloidopathy,4 this is apparent as the Brillouin peak detected in the mapping mode from any spatial location at low magnification (20×) arises from multiple contributions from different molecular constituents. An in-depth investigation of the molecular species involved in the mechanism of Aβ plaque formation is the first step to unravel the pathophysiology of this complex disease.…”

“…These studies have revealed the presence in many plaques of a lipid-rich layer surrounding a core that is made of intermolecular β-sheet structures of the Aβ peptide. We clarified the origin of this lipid layer in senile plaques within ex vivo hippocampal sections of Aβ-overexpressing TASTPM mouse brain (a model for familial Alzheimer's disease) using a combination of chemical imaging (FTIR spectroscopic imaging and Raman microscopy) and immunofluorescence imaging 4. The lipid layer stained positive for astrocytes co-localized with the lipid-loaded ring.…”