CSF Biomarkers for Alzheimer's Disease Diagnosis

Alzheimer's disease (AD) is the most common form of dementia that affects several million people worldwide. The major neuropathological hallmarks of AD are the presence of extracellular amyloid plaques that are composed of Aβ40 and Aβ42 and intracellular neurofibrillary tangles (NFT), which is composed of hyperphosphorylated protein Tau. While the amyloid plaques and NFT could define the disease progression involving neuronal loss and dysfunction, significant cognitive decline occurs before their appearance. Although significant advances in neuroimaging techniques provide the structure and physiology of brain of AD cases, the biomarker studies based on cerebrospinal fluid (CSF) and plasma represent the most direct and convenient means to study the disease progression. Biomarkers are useful in detecting the preclinical as well as symptomatic stages of AD. In this paper, we discuss the recent advancements of various biomarkers with particular emphasis on CSF biomarkers for monitoring the early development of AD before significant cognitive dysfunction

Comparison of brain development in sow-reared and artificially-reared piglets

IntroductionProvision of adequate nutrients is critical for proper growth and development of the neonate, yet the impact of breastfeeding versus formula feeding on neural maturation has yet to be fully determined. Using the piglet as a model for the human infant, our objective was to compare neurodevelopment of piglets that were either sow-reared or reared in an artificial setting. MethodsOver a 25-d feeding study, piglets (1.5 ± 0.2 kg initial bodyweight) were either sow-reared (SR; n = 10) with ad libitum intake, or artificially-reared (AR; n = 29) receiving an infant formula modified to mimic the nutritional profile and intake pattern of sow’s milk. At study conclusion, piglets were subjected to a standardized set of magnetic resonance imaging (MRI) procedures to quantify structure and composition of the brain.ResultsDiffusion tensor imaging, an MRI sequence that characterizes brain microstructure, revealed that SR piglets had greater (P < 0.05) average whole-brain fractional anisotropy, and lower (P < 0.05) mean and radial and axial diffusivity values compared with AR piglets, suggesting differences in white matter organization. Voxel-based morphometric analysis, a measure of white and gray matter volumes concentrations, revealed differences (P < 0.05) in bilateral development of gray matter clusters in the cortical brain regions of the AR piglets compared with SR piglets. Region of interest (ROI) analysis revealed larger (P < 0.05) whole brain volumes in SR animals compared with AR, and subcortical regions to be larger (P < 0.05) as a percentage of whole-brain volume in AR piglets compared with SR animals. Quantification of brain metabolites using magnetic resonance spectroscopy revealed SR piglets had higher (P < 0.05) concentrations of myo-inositol, glycerophosphocholine + phosphocholine, and creatine + phosphocreatine compared with AR piglets. However, glutamate + glutamine levels were higher (P < 0.05) in AR piglets when compared with SR animals. ConclusionOverall, increases in brain metabolite concentrations, coupled with greater FA values in white matter tracts and volume differences in gray matter of specific brain regions, suggest differences in myelin development and cell proliferation in SR vs. AR piglets

Edible Carrageenan Films Reinforced with Starch and Nanocellulose: Development and Characterization

Currently, from the sustainable development point of view, edible films are used as potential substitutes for plastics in food packaging, but their properties still have limitations and require further improvement. In this work, novel edible carrageenan films reinforced with starch granules and nanocellulose were developed and investigated for application as a bio-based food packaging system. The nanocellulose was used to improve film mechanical properties. Aloe vera gel was incorporated for antibacterial properties. Glycerol and sesame oil were added as plasticizers into the nanocomposite film to improve flexibility and moisture resistance. The interactions between charged polysaccharide functional groups were confirmed by FTIR spectroscopy. The migration of starch particles on the upper film surface resulting in increased surface roughness was demonstrated by scanning electron and atomic force microscopy methods. Thermogravimetric analysis showed that all films were stable up to 200 °C. The increase in nanocellulose content in films offered improved mechanical properties and surface hydrophilicity (confirmed by measurements of contact angle and mechanical properties). The film with a carrageenan/starch ratio of 1.5:1, 2.5 mL of nanocellulose and 0.5 mL of glycerol was chosen as the optimal. It demonstrated water vapor permeability of 6.4 × 10−10 g/(s m Pa), oil permeability of 2%, water solubility of 42%, and moisture absorption of 29%. This film is promising as a biodegradable edible food packaging material for fruits and vegetables to avoid plastic

Oligomerization prediction of Mel and PP.

<p>The intrinsic oligomerization ability of Mel and PP peptide was calculated (at pH 5.5) using Zyggregator software. The positive values (in red) represent aggregation propensity of corresponding amino acid.</p

Morphological characterization of Mel and PP oligomers.

<p>EM and AFM analysis were performed to visualize the morphology of two weeks incubated Mel and PP (in the presence of heparin). EM (left panel) and AFM (middle panel) images showing oligomer formation in the presence of heparin. The right panel shows 3D AFM height images of oligomer. Scale bars for EM images are 500 nm. Height scales for AFM images are also shown.</p

Hydrodynamic radius of oligomers.

<p>Dynamic light scattering (DLS) was performed to obtain the hydrodynamic radius (Rh) of peptide samples incubated for two weeks in presence and absence of heparin. The Rh values of peptides incubated in the presence of heparin increased considerably.</p

Structural characterization of Mel and PP.

<p><b>(A)</b> Structural model of Mel (red, PDB ID: 2MLT) and PP (blue, bovine PDB ID: 1BBA). <b>(B)</b> CD spectra of Mel and PP at day 0 (d0) and after 15 days (d15) in presence and absence of heparin. After the addition of heparin and subsequent incubation for two weeks, the secondary structure of PP remained mostly unchanged (helical). <b>(C)</b> FTIR spectra of two weeks incubated PP and Mel (in the absence and presence of heparin). Y-axis represents the absorbance (AU) and X-axis represents the wavenumber (cm^-1). Wavenumbers corresponding to the maximum absorbance are represented with arrow marks. Consistent with CD data, FTIR study also showed that in the presence of heparin, unstructured Mel transformed into helical conformation, whereas PP remained mostly helical both in presence and absence of heparin after incubation.</p

Hydrophobic surface exposure of oligomers.

<p>Hydrophobic surface exposure in terms of NR binding by Mel and PP samples, incubated for two weeks in presence and absence of heparin. The data suggesting increased hydrophobic surface exposure during heparin-induced peptide oligomerization.</p

Biophysical characterization of Mel in presence of SDS and liposome.

<p><b>(A)</b> CD spectroscopy showing the helical conformation of Mel after immediate addition of SDS (2.5 mM) in Gly-NaOH buffer (20 mM, pH 9.2). (<b>B)</b> Mel showing immediate conversion to helical conformation after addition of liposomes. <b>(C)</b> AFM images of Mel (incubated in the presence of SDS at 37°C) showing large globular oligomers and some fibrillar species (shown in the inset). <b>(D)</b> ThT binding of Mel after 5 days of incubation in the presence of SDS.</p