Here, we expounded the potential mechanism of GhCPC in regulating fiber development, although the findings of this study are similar to the Arabidopsis model, but the development of cotton fibers is much more complex than that of Arabidopsis trichomes. Compared to the complex and enormous regulatory network, short of enough evidences blocked the confirmation of the complex in fiber development. Elucidating the differences between these systems may further explain the specificity of the molecular regulatory mechanism of plant trichome development. There may be a question of whether results obtained from autopsy brains represent secondary alterations but not primary events in the pathological process of the diseases. In this study, to detect early changes in membrane lipids that trigger but not are caused by amyloid deposition, we carefully collected brain specimens at very early stage of amyloid deposition. In the initial profiling of gangliosides of this study, the levels of major gangliosides, including GD1bganglioside, did not decrease in sample P2 as was previously observed in AD brains. Thus, the alteration in the proportion of GD1b-ganglioside subspecies observed in this study was not likely attributable to amyloid deposition. Rather, the results of the addition of exogenous GD1b-gangliosides with different ceramide structure into samples P1 and P2 indicate that the altered expression of GD1b-ganglioside subspecies is a cause of enhanced A? assembly in the precuneus. At this point, it remains to be elucidated how A? assembly was enhanced on the reconstituted membrane of lipid sample P2. The significant inhibition of A? assembly by 4396C, a monoclonal antibody raised against GA?, suggested that A? assembly on the reconstituted membrane is likely through GA? generation. In terms of the mechanism underlying enhanced GA? generation on cellular membranes, it was previously suggested that local membrane lipids, including cholesterol and sphingomyelin, provide favorable milieu for GA? generation probably through facilitation of GM1-ganglioside clustering. However, no significant difference was observed in these lipids in this study. Thus, further driving force likely exists to facilitate GA? generation in the brain. Although further studies are required, it is intriguing to assume that GA? generation in the membranes is enhanced in a particular glycolipid condition, including the altered expression of GD1b-ganglioside subspecies as was observed in this study. In this regard, it is interesting to note that GM1-ganglioside appearance can be modulated by local glycolipid environment, especially by the neighboring GD1b-ganglioside. In this context, it is noteworthy that elimination of GD3-ganglioside synthase, causing deficiency of b-series of gangliosides, including GD1b-ganglioside, completely suppressed amyloid deposition in Alzheimer mouse model. At this stage, it remains to be clarified how a longer chain of fatty acid of GD1b-ganglioside can be involved in promoting the segregation of GM1-ganglioside. Besides a possibility of direct association with GM1-ganglioside, GD1b-ganglioside with a longer hydrophobic chain may have a unique effect on XAV939 distributor lateral phase separation of GM1-ganglioside through interaction with coexisting lipids such as phosphatidylcholine harboring variable length of acyl chains. In this study, we intend to search for the difference of lipid composition between precuneus and calcarine cortex, that is responsible for regional vulnerability/resistance to amyloid deposition. We have successfully identified imbalance of GD1b-ganglioside subspecies as a causative factor for the initiation of A? assembly in the precuneus. However, addition of GD1b to the lipids of sample C2, which increased the ratio of the level of GD1b to that of GD1b to mimic the condition of sample P2, failed to enhance A? assembly. This result implys that the alteration in the ratio of the level of GD1b to that of GD1b alone is not sufficient for overcoming the regional barrier to amyloid deposition between the precuneus and the calcarine cortex. An intriguing and challenging question of why calcarine cortex is SB431542 ALK inhibitor resistant to amyloid deposition still remains. How do we rationalize the unique alterations in the ganglioside expression pattern in the SPMs isolated from the precuneus?