methylcellulose and Alzheimer-Disease

Structural and functional abnormalities in the neurovascular unit (NVU) have been recently observed in Alzheimer's disease (AD). Statins, which are used clinically for reducing cholesterol levels, can also exert beneficial vascular actions, improve behavioral memory and reduce senile plaque (SP). Thus, we examined cognitive function, the serum level of lipids, senile plaque (SP), and the protective effects of statins on NVU disturbances in a mouse AD model. Amyloid precursor protein (APP) transgenic (Tg) mice were used as a model of AD. Atorvastatin (30 mg/kg/day, p.o.) or pitavastatin (3mg/kg/day, p.o.) were administered from 5 to 20 months of age. These 2 statins improved behavioral memory and reduced the numbers of SP at 15 and 20 M without affecting serum lipid levels. There was a reduction in immunopositive staining for N-acetyl glucosamine oligomer (NAGO) in the endothelium and in collagen IV in the APP vehicle (APP/Ve) group, with collagen IV staining most weakest near SP. There was also an increase in intensity and numbers of glial fibrillary acidic protein (GFAP) positive astrocytes, particularly around the SP, where MMP-9 was more strongly labeled. Double immunofluorescent analysis showed that astrocytic endfeet had detached from the capillary endothelium in the APP/Ve group. Overall, these data suggest that statins may have therapeutic potential for AD by protecting NVU.

Topics: Age Factors; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Analysis of Variance; Animals; Anticholesteremic Agents; Atorvastatin; Cholesterol; Collagen Type IV; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Glial Fibrillary Acidic Protein; Glucosamine; Heptanoic Acids; Humans; Matrix Metalloproteinase 9; Maze Learning; Methylcellulose; Mice; Mice, Transgenic; Mutation; Pyrroles; Quinolines

The preferential aggregation of Aβ1-42 in amyloid plaques is one of the major neuropathological events in Alzheimer's disease. This is accompanied by a relative reduction of the concentration of Aβ1-42 in the cerebrospinal fluid (CSF) of patients developing the signs of Alzheimer's disease. Here, we describe a microchip gel electrophoresis method in polydimethylsiloxane (PDMS) chip that enables rapid profiling of major Aβ peptides in cerebrospinal fluid. To control the electroosmotic flow (EOF) in the PDMS channel and also to reduce the adsorption of the peptides to the surface of the channel, a new double coating using poly(dimethylacrylamide-co-allyl glycidyl ether) (PDMA-AGE) and methylcellulose-Tween-20 was developed. With this method, separation of five synthetic Aβ peptides (Aβ1-37, Aβ1-38, Aβ1-39, Aβ1-40, and Aβ1-42) was achieved, and relative abundance of Aβ1-42 to Aβ1-37 could be calculated in different standard mixtures. We applied our method for profiling of Aβ peptides in CSF samples from nonAlzheimer patients and patients with Alzheimer's disease. Aβ peptides in the CSF samples were captured and concentrated using a microfluidic system in which magnetic beads coated with anti-Aβ were self-organized into an affinity microcolumn under the a permanent magnetic field. Finally, we could detect two Aβ peptides (Aβ1-40 and Aβ1-42) in the CSF samples.

Topics: Acrylic Resins; Alzheimer Disease; Amyloid beta-Peptides; Dimethylpolysiloxanes; Electrophoresis, Capillary; Humans; Methylcellulose; Microfluidic Analytical Techniques; Reproducibility of Results; Surface Properties