Triggering receptor expressed by myeloid cells 2 (TREM2), a member of immunoglobulin superfamily, has anti-inflammatory phagocytic function in myeloid cells. Several studies have shown that TREM2 gene variant rs75932628-T increased the risks for Alzheimer’s disease (AD), Parkinson’s disease, frontotemporal dementia, and amyotrophic lateral sclerosis. It has been suggested that the risks could be resulted from the loss of TREM2 function due to mutation. Indeed, new evidence showed that several mutations in the immunoglobulin-like V-region led to low cell-surface expression of TREM2 and reduced phagocytic functions. Because of emerging importance in understanding TREM2 expression and functions in human neurodegenerative diseases, we conducted biochemical and morphological studies of TREM2 expression in human postmortem temporal cortical samples from AD and normal cases. Increased expression of TREM2 protein was found to significantly correlate with increases of phosphorylatedtau and active caspase 3, a marker of apoptosis, and also loss of the presynaptic protein SNAP25. Strong intensities of TREM2 immunoreactivity were observed in the microglia associated with amyloid plaque and in neuritic pathology-enriched areas. Based on the findings that TREM2 expression correlated with neurodegenerative markers, further investigation on whether there is abnormality of TREM2 functions in AD brains with non-mutated TREM2 is needed.

The utility of plasma amyloid beta (Aβ) and tau levels for the clinical diagnosis of Alzheimer’s disease (AD) dementia has been controversial. The main objective of this study was to compare Aβ42 and tau levels measured by the ultra-sensitive immunomagnetic reduction (IMR) assays in plasma samples collected at the Banner Sun Health Institute (BSHRI) (United States) with those from the National Taiwan University Hospital (NTUH) (Taiwan). Significant increase in tau levels were detected in AD subjects from both cohorts, while Aβ42 levels were increased only in the NTUH cohort. A regression model incorporating age showed that tau levels identified probable ADs with 81 and 96% accuracy in the BSHRI and NTUH cohorts, respectively, while computed products of Aβ42 and tau increased the accuracy to 84% in the BSHRI cohorts. Using 382.68 (pg/ml)2 as the cut-off value, the product achieved 92% accuracy in identifying AD in the combined cohorts. Overall findings support that plasma Aβ42 and tau assayed by IMR technology can be used to assist in the clinical diagnosis of AD.

Prostate development is influenced by β-catenin signaling, but it is unclear which β-catenin activators are involved, where they are synthesized, and whether their mRNA abundance is influenced by androgens. We identified WNT/β-catenin-responsive β-galactosidase activity in the lower urogenital tract (LUT) of transgenic reporter mice, but β-galactosidase activity differed among the four mouse strains we examined. We used in situ hybridization to compare patterns of Wnts, r-spondins (Rspos, co-activators of β-catenin signaling), β-catenin-responsive mRNAs, and an androgen receptor-responsive mRNA in wild type fetal male, fetal female, and neonatal male LUT. Most Wnt and Rspo mRNAs were present in LUT during prostate development. Sexually dimorphic expression patterns were observed for WNT/β-catenin-responsive genes, and for Wnt2b, Wnt4, Wnt7a, Wnt9b, Wnt10b, Wnt11, Wnt16, and Rspo3 mRNAs. These results reveal sexual differences in WNT/β-catenin signaling in fetal LUT, supporting the idea that this pathway may be directly or indirectly responsive to androgens during prostate ductal development.

Epithelial-stromal interactions in the lower urogenital tract (LUT) are integral to prostatic and seminal vesicle development in males, vaginal and uterine development in females, and urethral development in both sexes. Gene expression profiling of isolated LUT stroma and epithelium has unraveled mechanisms of LUT development, but such studies are confounded by heterogeneous and ill-defined cell sub-populations contained within each tissue compartment. We used in situ hybridization to synthesize a high-resolution molecular atlas of 17 days post coitus fetal mouse LUT. We identified mRNAs that mark selective cell populations of the seminal vesicle, ejaculatory duct, prostate, urethra and vagina, subdividing these tissues into 16 stromal and 8 epithelial sub-compartments. These results provide a powerful tool for mapping LUT gene expression patterns and also reveal previously uncharacterized sub-compartments that may play mechanistic roles in LUT development of which we were previously unaware.

Fetal prostate development is initiated by androgens and patterned by androgen dependent and independent signals. How these signals integrate to control epithelial cell differentiation and prostatic bud patterning is not fully understood. To test the role of beta-catenin (Ctnnb1) in this process, we used a genetic approach to conditionally delete or stabilize Ctnnb1 in urogenital sinus (UGS) epithelium from which the prostate derives. Two opposing mechanisms of action were revealed. By deleting Ctnnb1, we found it is required for separation of UGS from cloaca, emergence or maintenance of differentiated UGS basal epithelium and formation of prostatic buds. By genetically inducing a patchy subset of UGS epithelial cells to express excess CTNNB1, we found its excess abundance increases Bmp expression and leads to a global impairment of prostatic bud formation. Addition of NOGGIN partially restores prostatic budding in UGS explants with excess Ctnnb1. These results indicate a requirement for Ctnnb1 in UGS basal epithelial cell differentiation, prostatic bud initiation and bud spacing and suggest some of these actions are mediated in part through activation of BMP signaling.