In-vivoandin-vitrotechniques used to investigate Alzheimer's disease

Abstract

Alzheimer's disease (AD) is one of the most common neurological diseases. It is characterized by the presence of β-amyloid peptides and highly phosphorylated tau proteins in the brain. The study of AD became more reliable with the development of new advances in both in-vivo (e.g. positron emission tomography, single-photon emission computed tomography, magnetic resonance imaging, functional magnetic resonance imaging, diffusion-weighted magnetic resonance imaging, and diffusion and perfusion magnetic resonance imaging) and in-vitro (e.g. circular dichroism, Fourier transform infrared spectroscopy, dye binding, transmission electron microscopy, scanning transmission electron microscopy, scanning tunnelling microscopy, atomic force microscopy and fluorescence resonance energy transfer) methods. These methods are used in the study of the pathogenesis and diagnosis of AD. Each method has its own advantages and limitations. This review explains the significance of different methods in understanding the pathogenesis of AD.

Effect of the fluorescent probes ThT and ANS on the mature amyloid fibrils

“…A wide range of physicochemical methods is used to study amyloid fibrils [13][14][15]. One of these approaches is the use of fluorescent probes that change their photophysical characteristics during its interaction with amyloid fibrils.…”

Ameliorating amyloid aggregation through osmolytes as a probable therapeutic molecule against Alzheimer's disease and type 2 diabetes

“…95 Atomistic simulations showed oligomerization as a result of anti-parallel b-sheet formation between C-terminal segments. The central [20][21][22][23][24][25][26][27][28][29] and Cterminal [30][31][32][33][34][35][36][37] segments aid in maintaining stable secondary structures and encouraging intermolecular interactions. The hydrophobic amino acids (I26 and L27) facilitate oligomeric conformations and help in the elongation of brils.…”

“…Both hIAPP and Ab are signicant components of amyloid plaques and share several features, including having similar b-sheet secondary structure conformations. 22 Several in vivo and in vitro studies have been performed in previous years to investigate AD 23,24 and T2D, [25][26][27] which have provided basic structural and overall dimensional details relating to IDPs but have rarely provided a unied image of the overall proteins. In order to understand the conformational dynamics of IDPs and the methods of structural ensemble recognition involving various binding neighbors and small molecule inhibitors, primarily, sampling techniques (knowledge and physics based) are used in silico accompanied by structural data obtained from experiments.…”

Recent Advances by In Silico and In Vitro Studies of Amyloid-β 1-42 Fibril Depicted a S-Shape Conformation

“…Because, despite of the many efforts made to observe and understand how the Aβ1-42 aggregation process is carried out in the human brain, some of them have not been successful. Currently, in vivo imaging studies and ex vivo histopathological studies only allow us to determine the presence of Aβ with an approximation of its state of aggregation [ 61 , 62 ]; but it is not possible to determine the atomic structure of the Aβ, nor to determine the aggregation stages in vivo, because the experimental conditions of extraction and purification of proteins could modify the quaternary structure [ 63 , 64 ]; therefore, it has not been possible to elucidate a quaternary structure for oligomers or fibrils in vivo in the brains of AD patients. Furthermore, it has not been confirmed whether the aggregation of Aβ in vitro is similar to those that occur in animal models and in patients.…”