A Comparison of Cerebrospinal Fluid Beta-Amyloid and Tau in Idiopathic Normal Pressure Hydrocephalus and Neurodegenerative Dementias.

Purpose: Idiopathic normal pressure hydrocephalus (iNPH) is the leading reversible cause of cognitive impairment and gait disturbance that has similar clinical manifestations and accompanies to major neurodegenerative disorders in older adults. We aimed to investigate whether cerebrospinal fluid (CSF) biomarker for Alzheimer's disease (AD) may be useful in the differential diagnosis of iNPH. Patients and Methods: Amyloid-beta (Aß) 42 and 40, total tau (t-tau), phosphorylated tau (p-tau) were measured via ELISA in 192 consecutive CSF samples of patients with iNPH (n=80), AD (n=48), frontotemporal dementia (FTD) (n=34), Lewy body diseases (LBDs) (n=30) consisting of Parkinson's disease dementia and dementia with Lewy bodies. Results: The mean age of the study population was 75.6±7.7 years, and 54.2% were female. CSF Aß42 levels were significantly higher, and p-tau and t-tau levels were lower in iNPH patients than in those with AD and LBDs patients. Additionally, iNPH patients had significantly higher levels of t-tau than those with FTD. Age and sex-adjusted multi-nominal regression analysis revealed that the odds of having AD relative to iNPH decreased by 37% when the Aß42 level increased by one standard deviation (SD), and the odds of having LBDs relative to iNPH decreased by 47%. The odds of having LBDs relative to iNPH increased 76% when the p-tau level increased 1SD. It is 2.5 times more likely for a patient to have LBD relative to NPH and 2.1 times more likely to have AD relative to iNPH when the t-tau value increased 1SD. Conclusion: Our results suggest that levels of CSF Aß42, p-tau, and t-tau, in particularly decreased t-tau, are of potential value in differentiating iNPH from LBDs and also confirm previous studies reporting t-tau level is lower and Aß42 level is higher in iNPH than in AD.

Blood-based microRNAs as diagnostic biomarkers to discriminate localized prostate cancer from benign prostatic hyperplasia and allow cancer-risk stratification.

Prostate cancer (PCa) is the second most diagnosed malignancy, and the leading cause of cancer-associated mortality among males. Prostate-specific antigen (PSA) has long been used for the detection of PCa. However, PSA levels increase in PCa and benign prostatic hyperplasia (BPH), and are associated with a poor disease outcome. Circulating microRNAs (miRNAs) have been determined to be highly stable in the circulation, and could be utilized as biomarkers to improve disease diagnosis and management. In the present study, the effectiveness of four PCa-associated miRNAs in the discrimination of PCa from BPH and the risk-stratification of PCa was assessed. The study included 100 participants: 35 patients with localized PCa, 35 patients with BPH and 30 healthy subjects. Patients with PCa were categorized based on their tumor stage (T), PSA level and Gleason score (GS) into low-(T 1/2, PSA <10 ng/ml or GS ≤7) and high-risk groups (T 3/4, PSA >20 ng/ml or GS ≥8). Reverse transcription-quantitative polymerase chain reaction was employed to assess the miRNA expression in peripheral blood samples. Significantly reduced expression of miR-15a, miR-126, miR-192 and miR-377 was observed in patients with PCa compared with patients with BPH and healthy subjects. In addition, the expression of the four miRNAs was lower in high-risk PCa patients than in low-risk PCa patients, with miR-126 being the most downregulated. The expression of the four miRNAs was also significantly and independently associated with PCa. Receiver operating characteristic curve analysis revealed a significant ability of the miRNAs to distinguish patients with PCa from those with BPH, patients with PCa from controls and low-risk PCa from high-risk PCa. These data suggested that expression of these miRNAs in the blood circulation may be promising, non-invasive biomarkers for the early detection of localized PCa, and for PCa risk stratification. Further validations of the clinical implementation of these results are warranted in a larger cohort.

Time- and oxygen-dependent expression and regulation of NDRG1 in human brain cancer cells.

N-myc downstream-regulated gene 1 (NDRG1) is a tumor suppressor with the potential to suppress metastasis, invasion and migration of cancer cells. It is regulated under stress conditions such as starvation or hypoxia. NDRG1 regulation is both induced and controlled by HIF-1α-dependent and -independent pathways under hypoxic conditions. However, there are profound differences in the way NDRG1 expression is regulated by HIF-1α and other transcription factors. Therefore, we aimed to define the time-dependent pattern of NDRG1 mRNA and protein expression in human glioblastoma cell lines in extreme hypoxia and after re-oxygenation as well as under normoxic conditions. Furthermore, we ascribe the regulation of NDRG1 to the transcription factors HIF-1α, SP1, CEBPα, YB-1 and Smad7 in a time-dependent manner. The human malignant glioma cell lines U87-MG, U373 and GaMG were cultured for 1, 6 and 24 h under hypoxic (0.1% O2) conditions and then they were re-oxygenated. The mRNA expression of NDRG1, HIF-1α SP1, CEBPα, YB-1 and Smad7 was measured using semi-quantitative RT-PCR analysis. Their protein expression was analyzed using western blotting. Our experiments revealed that long-term (24 h), but not short-term hypoxia led to the induction of NDRG1 expression in human glioma cell lines. NDRG1 expression was found to correlate with the protein expression of HIF-1α, SP1, CEBPα, YB-1 and Smad7. The present study suggests for the first time that SP1 regulates NDRG1 expression in glioma cells under hypoxia in a time-dependent manner along with HIF-1α, CEBPα, YB-1 and Smad7. These molecules, each separately or in combination, may possess the potential to become target molecules for antitumor therapeutic approaches particularly in human brain tumors.