The precuneus is a key region of the default mode network, which is selectively and early impaired in AD. Although the biological basis for the DMN at cellular level remains unknown, the regulatory mechanism of synaptic construction, including lipid composition, may be different from that in the DMN in other regions. Indeed, the characteristic features of cytoarchitectonic structures and synaptic connectivity were found in the precuneus. Notably, the alteration in the GD1b-ganglioside expression pattern observed in this study showed concordance with the change in the expression patterns of major gangliosides, including GD1b-ganglioside, with age. Thus, ageing-associated changes in ganglioside expression pattern may be accelerated somehow in the precuneus of individuals at risk of developing AD. It is also noteworthy that synthase for ceramide containing long chain fatty acid is selectively upregulated in the early stage of AD. Thus, it may be challenging and intriguing to explore the specificity of the precuneus from a viewpoint of the expression of different ceramide synthases in future studies. It remains unknown GSK1363089 whether the imbalance in the fatty-acid-chain length in gangliosides can be generally causative for amyloid deposition beyond the precuneus. Nevertheless, our results indicate that this imbalance is a strong bona fide driving force for initiating A? assembly in the precuneus. As suggested by accumulating evidence, sphingolipids, including complex gangliosides, may be critical players in AD. In addition, it should be elucidated in the future studies whether the change in the ganglioside compostion in the precuneus induce various neurobiological effects beyond initiation of A? assembly. Androgens are a class of steroid hormones that regulate prostate function, bone density, cardiac health, muscle mass, hair growth and fertility. Androgens diffuse through the plasma membrane and act via the intracellular androgen receptor to alter gene expression and intracellular signaling pathways in target cells. The two major functional androgens in mammals are testosterone and Y-27632 dihydrochloride 129830-38-2 dihydrotestosterone. Because of the high levels of testosterone produced locally by the Leydig cells within the testis, this form of androgen is the major regulator of testis functions and the male reproductive tract. In most other tissues, the lower concentrations of testosterone present allow DHT to be the major acting androgen because DHT has a 10-fold greater affinity for AR than testosterone. There are 2 two pathways by which androgens act to regulate cellular function. In the classical pathway, androgen interacts with AR in the cytoplasm that then translocates to the nucleus where it binds androgen response element DNA sequences and directly regulates gene expression. In the non-classical pathway, androgens act via AR, in the cytoplasm, to rapidly activate kinase cascades or alter intracellular levels. The resulting phosphorylation changes alter the activities of target proteins that can cause immediate changes in cellular physiology as well as indirect or delayed effects including altered gene expression. Non-classical AR action has been documented in numerous cell types including skeletal muscle fibers, cardiac myocytes, neurons, prostate cancer cells, macrophages and T-cells as well as Sertoli cells. In males, testosterone is essential for proper sexual differentiation and the maintenance of spermatogenesis, which is the progression of germ cell development into mature sperm. Functional androgen receptor is not expressed in germ cells. However, testosterone support for germ cell development occurs via the Leydig, peritubular myoid cells and Sertoli cells that express AR. Sertoli cells are the major transducers of testosterone signals to the adjacent germ cells. Assessments of spermatogenesis after testosterone deprivation studies and examinations of Sertoli cell specific AR knock out mice have shown that testosterone signaling through the AR in Sertoli cells is required to maintain the blood testis barrier for the completion of meiosis, maintaining the attachment of germ cells to Sertoli cells and the release of mature spermatozoa.