Abstract
Definite Alzheimer's disease (AD) diagnosis is commonly done on ex vivo brain tissue using immuno-histochemical staining to visualize amyloid-beta (Aβ) aggregates, also known as Aβ plaques. Raman spectroscopy has shown its potential for non-invasive and label-free determination of bio-molecular compositions, aiding the post-mortem diagnosis of pathological tissue. Here, we investigated whether conventional Raman spectroscopy could be used for the detection of amyloid beta deposits in fixed, ex vivo human brain tissue, taken from the frontal cortex region. We examined the spectra and spectral maps of three severe AD cases and two healthy control cases and compared their spectral outcome among each other as well as to recent results in the literature obtained with various spectroscopic techniques. After hyperspectral Raman mapping, Aβ plaques were visualized using Thioflavin-S staining on the exact same tissue sections. As a result, we show that tiny diffuse or tangled-like morphological structures, visible under microscopic conditions on unstained tissue and often but erroneously assumed to be deposits of Aβ, are instead usually an aggregation of highly auto-fluorescent lipofuscin granulates without any, or limited, plaque or plaque-like association. The occurrence of these auto-fluorescent particles is equally distributed in both AD and healthy control cases. Therefore, they cannot be used as possible criteria for Alzheimer's disease diagnosis. Furthermore, a unique plaque-specific/Aβ spectrum could not be determined even after possible spectral interferences were carefully removed.
Highlights
Aside from intracellular phosphorylated tau deposits,[1,2] extracellular accumulation of amyloid-beta into plaques is known as the main pathological hallmark in ex vivo brain tissue for the diagnosis of Alzheimer’s disease.[3,4,5,6] Aβ peptides are molecular chains split off from the amyloid precursor protein (APP) and they adopt predominantly a poorly soluble β-sheet conformation
As state of the art diagnosis, Aβ is targeted in cerebrospinal fluid (CSF) analysis[7,8] and positron emission tomography (PET) is performed on in vitro and in vivo brain tissue.[9,10]
Post mortem brain tissue was obtained from the Netherlands Brain Bank (NBB; Amsterdam, the Netherlands)
Summary
Aside from intracellular phosphorylated tau ( pTau) deposits,[1,2] extracellular accumulation of amyloid-beta into plaques is known as the main pathological hallmark in ex vivo brain tissue for the diagnosis of Alzheimer’s disease.[3,4,5,6] Aβ peptides are molecular chains split off from the amyloid precursor protein (APP) and they adopt predominantly a poorly soluble β-sheet conformation. As state of the art diagnosis, Aβ is targeted in cerebrospinal fluid (CSF) analysis[7,8] and positron emission tomography (PET) is performed on in vitro and in vivo brain tissue.[9,10] blood components and derivatives have been investigated for potential diagnosis of Alzheimer’s disease using spectroscopic techniques.[11,12,13,14] The former mentioned methods are, at least, partially invasive, 1724 | Analyst, 2020, 145, 1724–1736 Paper. A very small fraction of the light undergoes inelastic scattering according to the vibrational modes of the irradiated molecules, providing a spectral fingerprint.[28,29,30,31]
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