An approach for in-situ detection of gold colloid aggregates amyloid formations within the hippocampus of the Cohen's Alzheimer's disease rat model by surface enhanced raman scattering methods

Abstract

Background: Amyloid beta (Aβ) peptides, such as Aβ_1-40 or Aβ_1-42 are regarded as hallmark neuropathological biomarkers associated with Alzheimer's disease (AD). The formation of an aggregates by Aβ_1-40 or Aβ_1-42-coated gold nano-particles are hypothesized to contain conformation of Aβ oligomers, which could exist only at an initial stage of fibrillogenesis.

New method: The attempt of in-situ detection of externally initiated gold colloid (ca. 80 nm diameter) aggregates in the middle section of the hippocampus of the Long Evans Cohen's Alzheimer's disease rat model was conducted through the Surface Enhanced Raman Scattering (SERS) method.

Results: The SERS spectral features contained modes associated with β-sheet interactions and a significant number of modes that were previously reported in SERS shifts for Alzheimer diseased rodent and human brain tissues; thereby, strongly implying a containment of amyloid fibrils. The spectral patterns were further examined and compared with those collected from in-vitro gold colloid aggregates which were formed from Aβ_1-40 - or Aβ_1-42 -coated 80 nm gold colloid under pH ∼4, pH ∼7, and pH ∼10, and the best matched datasets were found with that of the aggregates of Aβ_1-42 -coated 80 nm gold colloid at ∼pH 4.0. The morphology and physical size of this specific gold colloid aggregate was clearly different from those found in-vitro.

Comparison with existing method(s): The amyloid fibril with a β-sheet conformation identified in previously reported in AD mouse/human brain tissues was involved in a formation of the gold colloid aggregates. However, to our surprise, best explanation for the observed SERS spectral features was possible with those in vitro Aβ_1-42 -coated 80 nm gold colloid under pH ∼4.

Conclusions: A formation of gold colloid aggregates was confirmed in the AD rat hippocampal brain section with unique physical morphology compared to those observed in in-vitro Aβ_1-42 or Aβ_1-40 mediated gold colloid aggregates. It was concluded that a β-sheet conformation identified in previously reported in AD mouse/human brain tissues was in volved in a formation of the gold colloid aggregates.

Keywords: Alzheimer's disease (AD); Cohen's Alzheimer's disease model; Gold nano-particles; Protein corona; Surface Enhanced Raman Scattering (SERS); Surface plasmon.